Potassium ion

evidence_access

Primary abstract

experimental_model

Purified human enzyme and potassium-bound structures.

limitations

Assay activation is not proof that extra potassium accelerates isoleucine breakdown in a potassium-replete person.

nutrient_topic

L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine

plain_language

Potassium changed the activity of an enzyme shared by isoleucine and ketone processing.

primary_references

Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17371050/ · DOI 10.1021/bi6026192

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 234–240

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme and potassium-bound structures. · source_derived_draft · unverified_draft

## isoleucine-acat1-potassium Potassium changed the activity of an enzyme shared by isoleucine and ketone processing. Increasing KCl from 0 to 40 mM increased purified human T2 turnover approximately threefold for both acetoacetyl-CoA and 2-methylacetoacetyl-CoA. Model: Purified human enzyme and potassium-bound structures. Limitations: Assay activation is not proof that extra potassium accelerates isoleucine breakdown in a potassium-replete person. Evidence access: Primary abstract Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17371050/ · DOI 10.1021/bi6026192

cross_nutrient

Potassium and magnesium contribute distinct sites in a thiamine-dependent branched-chain ketoacid enzyme.

experimental_model

Human E1b crystallography, deposited structure 1DTW.

limitations

A structural potassium site is not a potassium-intake response experiment.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

Potassium also helps shape this B1-dependent enzyme; the metal roles are distinct.

primary_references

[aevarsson-2000-bckdh] Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease (2000). https://pubmed.ncbi.nlm.nih.gov/10745006/ DOI: 10.1016/s0969-2126(00)00105-2

tissue_or_cell_type

Recombinant E1b crystal

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 650–660

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human E1b crystallography, deposited structure 1DTW. · source_derived_draft · unverified_draft

### mg-bckdh-potassium-site Human E1b contains potassium sites, including one organizing a loop near the ThDP cofactor. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium also helps shape this B1-dependent enzyme; the metal roles are distinct. organism: Homo sapiens tissue_or_cell_type: Recombinant E1b crystal experimental_model: Human E1b crystallography, deposited structure 1DTW. limitations: A structural potassium site is not a potassium-intake response experiment. cross_nutrient: Potassium and magnesium contribute distinct sites in a thiamine-dependent branched-chain ketoacid enzyme. [aevarsson-2000-bckdh] Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease (2000). https://pubmed.ncbi.nlm.nih.gov/10745006/ DOI: 10.1016/s0969-2126(00)00105-2

cross_nutrient

Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.

experimental_model

Pig-kidney enzyme stopped-flow RH421 fluorescence; sequential ATP then KCl mixing.

limitations

Stopped-flow assay; no dietary or magnesium-depletion intervention.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Sus scrofa

plain_language

Potassium promotes the phosphate-removal part of the pump cycle.

primary_references

[kane-1998-nka] Dephosphorylation kinetics of pig kidney Na+,K+-ATPase (1998). https://pubmed.ncbi.nlm.nih.gov/9521778/ DOI: 10.1021/bi972813e

tissue_or_cell_type

Kidney enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 807–817

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pig-kidney enzyme stopped-flow RH421 fluorescence; sequential ATP then KCl mixing. · source_derived_draft · unverified_draft

### mg-nka-potassium-dephosphorylation Adding KCl after ATP phosphorylation accelerated dephosphorylation of pig-kidney Na/K-ATPase. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium promotes the phosphate-removal part of the pump cycle. organism: Sus scrofa tissue_or_cell_type: Kidney enzyme experimental_model: Pig-kidney enzyme stopped-flow RH421 fluorescence; sequential ATP then KCl mixing. limitations: Stopped-flow assay; no dietary or magnesium-depletion intervention. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [kane-1998-nka] Dephosphorylation kinetics of pig kidney Na+,K+-ATPase (1998). https://pubmed.ncbi.nlm.nih.gov/9521778/ DOI: 10.1021/bi972813e

cross_nutrient

magnesium -> potassium

experimental_model

Heterologous channel expression and patch-clamp

exposure

External K tested at 110, 11 and 1.1 mM; experimental concentrations, not dietary targets.

limitations

Excised-patch channel behavior does not quantify whole-body potassium loss in humans.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Xenopus laevis host; mammalian ROMK channel

plain_language

The potassium concentration outside the cell changes how strongly inside Mg restrains potassium exit.

primary_references

[yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617

tissue_or_cell_type

Oocyte membrane

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 116–127

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous channel expression and patch-clamp · source_derived_draft · unverified_draft

### mg-romk2-low-external-k-enhances-block Lower external K+ increased the apparent affinity of cytoplasmic Mg2+ block of rat ROMK2 and permitted block over physiologically relevant negative voltages. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The potassium concentration outside the cell changes how strongly inside Mg restrains potassium exit. organism: Xenopus laevis host; mammalian ROMK channel tissue_or_cell_type: Oocyte membrane experimental_model: Heterologous channel expression and patch-clamp limitations: Excised-patch channel behavior does not quantify whole-body potassium loss in humans. cross_nutrient: magnesium -> potassium exposure: External K tested at 110, 11 and 1.1 mM; experimental concentrations, not dietary targets. [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617

cross_nutrient

Potassium/sodium-B6 enzyme kinetics.

evidence_location

Full text: Metal binding and enzyme activity; Figure 1

experimental_model

Purified recombinant human PDXK kinetics and crystallography.

exposure

Kinetic assays at pH 7.3.

limitations

Lower Km is not a direct binding constant; results do not define dietary sodium/potassium effects.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

Potassium and sodium affect different kinetic properties.

primary_references

[safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107

tissue_or_cell_type

Purified human enzyme

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 203–215

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PDXK kinetics and crystallography. · source_derived_draft · unverified_draft

### b6-transport-pdxk-k-na Human PDXK showed lower substrate Km with potassium than sodium, whereas sodium supported over twice the maximal activity. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium and sodium affect different kinetic properties. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human PDXK kinetics and crystallography. limitations: Lower Km is not a direct binding constant; results do not define dietary sodium/potassium effects. exposure: Kinetic assays at pH 7.3. evidence_location: Full text: Metal binding and enzyme activity; Figure 1 cross_nutrient: Potassium/sodium-B6 enzyme kinetics. [safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107

evidence_span

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experimental_model

Whole-cell current reversal measurements

exposure

Ion substitution, intracellular sodium/glutamate and extracellular potassium

limitations

Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Mammalian GLT-1 expressed in Chinese hamster ovary cells

plain_language

Changing the ion gradients can reverse a transporter that normally clears glutamate.

primary_references

[sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998

tissue_or_cell_type

Plasma membrane

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 382–393

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-cell current reversal measurements · source_derived_draft · unverified_draft

### sodium-glt1-reversal Increasing extracellular potassium around cells loaded with sodium and glutamate evoked an outward, blocker-sensitive reversed transport current. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the ion gradients can reverse a transporter that normally clears glutamate. organism: Mammalian GLT-1 expressed in Chinese hamster ovary cells tissue_or_cell_type: Plasma membrane experimental_model: Whole-cell current reversal measurements limitations: Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result. exposure: Ion substitution, intracellular sodium/glutamate and extracellular potassium evidence_span: {"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"} [sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998

evidence_access

Primary abstract

experimental_model

Dog kidney Na/K-ATPase binding experiments.

limitations

Effect was not appreciable under the manganese condition; not evidence that dietary potassium necessarily increases toxicity.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

Potassium can shift the pump toward an inhibitor-sensitive state.

primary_references

Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 238–244

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Dog kidney Na/K-ATPase binding experiments. · source_derived_draft · unverified_draft

## vanadium-pump-potassium Potassium can shift the pump toward an inhibitor-sensitive state. In magnesium-containing medium, potassium increased vanadate binding and lowered its Kd to about 11 nM without changing maximum binding. Model: Dog kidney Na/K-ATPase binding experiments. Limitations: Effect was not appreciable under the manganese condition; not evidence that dietary potassium necessarily increases toxicity. Evidence access: Primary abstract Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

evidence_access

Primary full text

experimental_model

Mouse macrophages; 130 mM KCl experimental condition.

limitations

Not a potassium supplement treatment; no specific channel identity was established.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

The potassium gradient gates this inflammatory response.

primary_references

Activation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 480–486

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophages; 130 mM KCl experimental condition. · source_derived_draft · unverified_draft

## silica-potassium-gate The potassium gradient gates this inflammatory response. High extracellular potassium blocked silica-induced caspase-1 processing and IL-1 beta release, including during low-dose uptake blockade. Model: Mouse macrophages; 130 mM KCl experimental condition. Limitations: Not a potassium supplement treatment; no specific channel identity was established. Evidence access: Primary full text Activation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281

evidence_access

Primary abstract

experimental_model

Purified human MAT2A crystallography and kinetic study.

limitations

Does not show that extra potassium increases methylation in potassium-replete humans.

nutrient_topic

L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine

plain_language

Potassium participates directly in the enzyme chemistry.

primary_references

Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33656855/ · DOI 10.1021/acs.biochem.0c00998

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 140–146

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human MAT2A crystallography and kinetic study. · source_derived_draft · unverified_draft

## methionine-mat-potassium Potassium participates directly in the enzyme chemistry. An essential potassium ion contacted the beta-phosphoryl oxygen in the human MAT2A catalytic-site ligand structure. Model: Purified human MAT2A crystallography and kinetic study. Limitations: Does not show that extra potassium increases methylation in potassium-replete humans. Evidence access: Primary abstract Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33656855/ · DOI 10.1021/acs.biochem.0c00998

evidence_span

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experimental_model

Crystallography and mutagenesis

exposure

Cesium surrogate and potassium-inhibition assays

limitations

Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing.

nutrient_topic

Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride

organism

Human WNK1/WNK3 constructs

plain_language

Potassium can regulate WNK1 directly as well as through changes in cell voltage and chloride.

primary_references

[chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825

tissue_or_cell_type

Purified kinase domains

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 367–378

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography and mutagenesis · source_derived_draft · unverified_draft

### chloride-wnk1-potassium WNK1 E388 mutations reduced potassium inhibition while retaining kinase activity. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium can regulate WNK1 directly as well as through changes in cell voltage and chloride. organism: Human WNK1/WNK3 constructs tissue_or_cell_type: Purified kinase domains experimental_model: Crystallography and mutagenesis limitations: Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing. exposure: Cesium surrogate and potassium-inhibition assays evidence_span: {"source_cache": "artifacts/chloride-research/42186973.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa", "start_char": 0, "end_char": 1266, "text_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa"} [chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825

evidence_span

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experimental_model

Crystallography and mutagenesis

exposure

Cesium surrogate and potassium-inhibition assays

limitations

Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing.

nutrient_topic

Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride

organism

Human WNK1/WNK3 constructs

plain_language

The direct potassium-sensitive route also has evidence in WNK3.

primary_references

[chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825

tissue_or_cell_type

Purified kinase domains

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 380–391

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography and mutagenesis · source_derived_draft · unverified_draft

### chloride-wnk3-potassium Mutation of the corresponding WNK3 E314 site reduced potassium inhibition. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The direct potassium-sensitive route also has evidence in WNK3. organism: Human WNK1/WNK3 constructs tissue_or_cell_type: Purified kinase domains experimental_model: Crystallography and mutagenesis limitations: Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing. exposure: Cesium surrogate and potassium-inhibition assays evidence_span: {"source_cache": "artifacts/chloride-research/42186973.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa", "start_char": 0, "end_char": 1266, "text_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa"} [chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825

experimental_model

Mouse isolated capillary-arteriole preparations and in-vivo imaging.

exposure

Local 10 mmol/L K application.

limitations

Local experimental potassium exposure, not dietary supplementation.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

Brain capillaries can send an electrical signal upstream to their supplying arteriole.

primary_references

[k-longden2017] Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow (2017). https://pubmed.ncbi.nlm.nih.gov/28319610/ DOI: 10.1038/nn.4533

tissue_or_cell_type

Brain capillary endothelium and upstream arterioles

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1604–1614

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse isolated capillary-arteriole preparations and in-vivo imaging. · source_derived_draft · unverified_draft

### k-capillary-kir21-sensing Local potassium stimulated Kir2.1-dependent capillary signaling; endothelial Kir2.1 deletion abolished the tested potassium-evoked upstream dilation. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Brain capillaries can send an electrical signal upstream to their supplying arteriole. organism: Mus musculus tissue_or_cell_type: Brain capillary endothelium and upstream arterioles experimental_model: Mouse isolated capillary-arteriole preparations and in-vivo imaging. limitations: Local experimental potassium exposure, not dietary supplementation. exposure: Local 10 mmol/L K application. [k-longden2017] Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow (2017). https://pubmed.ncbi.nlm.nih.gov/28319610/ DOI: 10.1038/nn.4533

experimental_model

Same CKD crossover.

limitations

Cannot infer long-term food effects.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

An alkalizing potassium salt did not remove the potassium rise in this study.

primary_references

[k-ckd-salts2026] Randomized Cross-Over Trial of Electrolyte, Acid-Base and Blood Pressure Effects of Salt Supplements in CKD (2026). https://pubmed.ncbi.nlm.nih.gov/42381762/ DOI: 10.1016/j.ekir.2026.106619

tissue_or_cell_type

Plasma

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1674–1683

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same CKD crossover. · source_derived_draft · unverified_draft

### k-ckd-salts-potassium-not-rescued-by-alkali All three potassium salts increased plasma potassium despite their different acid-base effects. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An alkalizing potassium salt did not remove the potassium rise in this study. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Same CKD crossover. limitations: Cannot infer long-term food effects. [k-ckd-salts2026] Randomized Cross-Over Trial of Electrolyte, Acid-Base and Blood Pressure Effects of Salt Supplements in CKD (2026). https://pubmed.ncbi.nlm.nih.gov/42381762/ DOI: 10.1016/j.ekir.2026.106619

cross_nutrient

Potassium transport depends jointly on sodium and magnesium-supported ATP chemistry.

experimental_model

Resealed human erythrocyte ghosts; sided ion substitutions.

limitations

Sided activation adds to existing catalog flux/phosphorylation records; MgATP-only binding is not asserted.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Human

plain_language

Potassium outside and sodium inside activate complementary sides of the pump.

primary_references

[garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

tissue_or_cell_type

Erythrocyte membrane

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 575–585

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Resealed human erythrocyte ghosts; sided ion substitutions. · source_derived_draft · unverified_draft

### k-pump-extracellular-activation External potassium supported ouabain-sensitive ATP hydrolysis when erythrocyte ghosts contained sodium, ATP and magnesium. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium outside and sodium inside activate complementary sides of the pump. organism: Human tissue_or_cell_type: Erythrocyte membrane experimental_model: Resealed human erythrocyte ghosts; sided ion substitutions. limitations: Sided activation adds to existing catalog flux/phosphorylation records; MgATP-only binding is not asserted. cross_nutrient: Potassium transport depends jointly on sodium and magnesium-supported ATP chemistry. [garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

experimental_model

Myogenic tone at 60/90 mmHg, nitric oxide and prostanoid pathways blocked.

limitations

Preparation and tone differ from earlier work; record scope rather than inventing an unexplained contradiction.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rattus norvegicus

plain_language

Potassium is not a universal explanation for endothelial relaxation.

primary_references

[k-brochet2014] A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries (2014). https://pubmed.ncbi.nlm.nih.gov/25372386/ DOI: 10.1371/journal.pone.0111977

tissue_or_cell_type

Mesenteric resistance arteries

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1627–1636

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Myogenic tone at 60/90 mmHg, nitric oxide and prostanoid pathways blocked. · source_derived_draft · unverified_draft

### k-vascular-edhf-context-boundary In pressurized rat mesenteric arteries, raised potassium did not reliably reproduce acetylcholine-evoked EDHF relaxation or hyperpolarization. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium is not a universal explanation for endothelial relaxation. organism: Rattus norvegicus tissue_or_cell_type: Mesenteric resistance arteries experimental_model: Myogenic tone at 60/90 mmHg, nitric oxide and prostanoid pathways blocked. limitations: Preparation and tone differ from earlier work; record scope rather than inventing an unexplained contradiction. [k-brochet2014] A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries (2014). https://pubmed.ncbi.nlm.nih.gov/25372386/ DOI: 10.1371/journal.pone.0111977

cross_nutrient

Potassium/sodium pump and potassium channels -> vessel response.

experimental_model

Isolated rat artery electrophysiology.

limitations

Channel family inference; not every artery or potassium concentration responds this way.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rattus norvegicus

plain_language

A modest local potassium rise can relax a vessel under particular conditions.

primary_references

[k-edwards1998] K+ is an endothelium-derived hyperpolarizing factor in rat arteries (1998). https://pubmed.ncbi.nlm.nih.gov/9834033/ DOI: 10.1038/24388

tissue_or_cell_type

Arterial smooth muscle

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1592–1602

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated rat artery electrophysiology. · source_derived_draft · unverified_draft

### k-vascular-pump-kir-relaxation Small extracellular potassium elevations relaxed the studied rat arteries through ouabain/barium-sensitive pump and inward-rectifier pathways. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A modest local potassium rise can relax a vessel under particular conditions. organism: Rattus norvegicus tissue_or_cell_type: Arterial smooth muscle experimental_model: Isolated rat artery electrophysiology. limitations: Channel family inference; not every artery or potassium concentration responds this way. cross_nutrient: Potassium/sodium pump and potassium channels -> vessel response. [k-edwards1998] K+ is an endothelium-derived hyperpolarizing factor in rat arteries (1998). https://pubmed.ncbi.nlm.nih.gov/9834033/ DOI: 10.1038/24388

cross_nutrient

Extracellular K controls the intracellular chloride signal.

evidence_location

Figure 6A-B; Figure S5.

experimental_model

Cell culture and Kir4.1 mutant comparisons

limitations

HEK chloride and WNK expression differ from native DCT.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens; Mus musculus cell lines

plain_language

A change outside the cell can change chloride inside, connecting potassium sensing to salt transport.

primary_references

[terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006

tissue_or_cell_type

HEK293 and mDCT cells

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 125–136

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell culture and Kir4.1 mutant comparisons · source_derived_draft · unverified_draft

### renal-low-external-k-lowers-cell-chloride Low-K medium lowered intracellular chloride in HEK293 and mDCT cells; depolarizing Kir4.1 mutants increased it. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A change outside the cell can change chloride inside, connecting potassium sensing to salt transport. organism: Homo sapiens; Mus musculus cell lines tissue_or_cell_type: HEK293 and mDCT cells experimental_model: Cell culture and Kir4.1 mutant comparisons limitations: HEK chloride and WNK expression differ from native DCT. cross_nutrient: Extracellular K controls the intracellular chloride signal. evidence_location: Figure 6A-B; Figure S5. [terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006

cross_nutrient

Luminal K availability supports coupled sodium/chloride reabsorption.

evidence_location

Primary abstract; ion-removal and conductance-blocking experiments.

experimental_model

Isolated perfused tubules; K removal and barium blockade

limitations

Electrical surrogate; the study predates molecular identification of NKCC2 and ROMK.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Oryctolagus cuniculus

plain_language

Recycled luminal potassium supports sodium and chloride uptake in the thick ascending limb.

primary_references

[greger-1981-luminal-k] Presence of luminal K+, a prerequisite for active NaCl transport in the cortical thick ascending limb of Henle's loop of rabbit kidney (1981). https://pubmed.ncbi.nlm.nih.gov/7322839/ DOI: 10.1007/BF00584588

tissue_or_cell_type

Cortical thick ascending limb

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 447–458

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated perfused tubules; K removal and barium blockade · source_derived_draft · unverified_draft

### renal-luminal-k-enables-tal-salt-transport Removing luminal K reduced active transport current in rabbit cortical TAL; combining K removal with luminal barium nearly abolished it. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Recycled luminal potassium supports sodium and chloride uptake in the thick ascending limb. organism: Oryctolagus cuniculus tissue_or_cell_type: Cortical thick ascending limb experimental_model: Isolated perfused tubules; K removal and barium blockade limitations: Electrical surrogate; the study predates molecular identification of NKCC2 and ROMK. cross_nutrient: Luminal K availability supports coupled sodium/chloride reabsorption. evidence_location: Primary abstract; ion-removal and conductance-blocking experiments. [greger-1981-luminal-k] Presence of luminal K+, a prerequisite for active NaCl transport in the cortical thick ascending limb of Henle's loop of rabbit kidney (1981). https://pubmed.ncbi.nlm.nih.gov/7322839/ DOI: 10.1007/BF00584588

cross_nutrient

High K can suppress the sodium/chloride transporter through additional signaling.

evidence_location

Primary abstract; low extracellular chloride and DIDS experiments.

experimental_model

Perfused kidney and kidney slices

limitations

Pharmacological/ionic tests do not prove every chloride-sensitive step is absent.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

The rapid high-potassium response can persist when tested chloride movements are disrupted.

primary_references

[penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504

tissue_or_cell_type

Native DCT

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 229–240

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused kidney and kidney slices · source_derived_draft · unverified_draft

### renal-native-high-k-cl-independent-ncc-off High-K-induced NCC dephosphorylation persisted during low extracellular chloride or chloride-channel blockade in mouse kidney preparations. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The rapid high-potassium response can persist when tested chloride movements are disrupted. organism: Mus musculus tissue_or_cell_type: Native DCT experimental_model: Perfused kidney and kidney slices limitations: Pharmacological/ionic tests do not prove every chloride-sensitive step is absent. cross_nutrient: High K can suppress the sodium/chloride transporter through additional signaling. evidence_location: Primary abstract; low extracellular chloride and DIDS experiments. [penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504

cross_nutrient

K concentration regulates sodium/chloride transport via chloride-sensitive signaling.

evidence_location

Abstract and Results; low chloride and DIDS comparisons.

experimental_model

Perfused kidney and kidney slices

limitations

Acute bath/perfusate manipulation is not whole-body potassium depletion.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

The low-potassium signal needs chloride movement to increase the transporter phosphate signal.

primary_references

[penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504

tissue_or_cell_type

Native DCT

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 216–227

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused kidney and kidney slices · source_derived_draft · unverified_draft

### renal-native-low-k-requires-chloride-flux In native mouse kidney preparations, low extracellular K increased NCC phosphorylation through chloride-conductance-dependent SPAK/OSR1 signaling. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The low-potassium signal needs chloride movement to increase the transporter phosphate signal. organism: Mus musculus tissue_or_cell_type: Native DCT experimental_model: Perfused kidney and kidney slices limitations: Acute bath/perfusate manipulation is not whole-body potassium depletion. cross_nutrient: K concentration regulates sodium/chloride transport via chloride-sensitive signaling. evidence_location: Abstract and Results; low chloride and DIDS comparisons. [penton-2016-native-potassium-switch] Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl--dependent and independent mechanisms (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5088235/ DOI: 10.1113/JP272504

evidence_span

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experimental_model

Recombinant human enzyme and complementation of yeast ino1 deletion

exposure

Substrate, NAD+, cation and valproate experiments

limitations

Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Human protein expressed in bacteria and yeast

plain_language

Potassium can influence this enzyme in a test tube; that does not demonstrate a benefit from extra dietary potassium.

primary_references

[ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200

tissue_or_cell_type

Purified enzyme; yeast cultures

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 197–208

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme and complementation of yeast ino1 deletion · source_derived_draft · unverified_draft

### ino-isyna-potassium K+ was among the stronger cation activators of purified human ISYNA1 under the tested assay conditions. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium can influence this enzyme in a test tube; that does not demonstrate a benefit from extra dietary potassium. organism: Human protein expressed in bacteria and yeast tissue_or_cell_type: Purified enzyme; yeast cultures experimental_model: Recombinant human enzyme and complementation of yeast ino1 deletion limitations: Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold. exposure: Substrate, NAD+, cation and valproate experiments evidence_span: {"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"} [ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200

cross_nutrient

true

evidence_location

Primary PDF pp.1643–1654; design, results and discussion.

experimental_model

Historical controlled feeding study in six adult male volunteers; two diet-only deficient, two deficient plus antagonist, two supplemented controls

exposure

Tube-fed experimental formula; controls received pantothenic acid 20 mg/day, antagonist pair 750 then 1000 mg/day omega-methyl compound; recovery included 4000 mg/day vitamin. One man per pair received 10.8 mEq/day extra potassium.

limitations

Very small historical cohort; other vitamins and formula composition were controlled imperfectly. Diet-only and antagonist groups are distinguished. Measurements do not establish a universal symptom, adrenal disease mechanism or cellular CoA threshold. No full potassium balance study was done; the record does not establish B5-dependent renal potassium wasting or refractory potassium repletion.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

Potassium supply affected the blood result independently of how the B5 groups were assigned.

primary_references

[b5-clin-hodges1958] Pantothenic acid deficiency in man. (1958). https://pubmed.ncbi.nlm.nih.gov/13587673/ DOI: 10.1172/jci103756

tissue_or_cell_type

Whole-person symptoms, serum and urine

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1187–1199

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical controlled feeding study in six adult male volunteers; two diet-only deficient, two deficient plus antagonist, two supplemented controls · source_derived_draft · unverified_draft

### b5-clin-potassium-context On the experimental formula, men receiving 20.5 mEq/day potassium had serum potassium near the lower normal limit, while an extra 10.8 mEq/day maintained somewhat higher values across the paired B5 regimens. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium supply affected the blood result independently of how the B5 groups were assigned. organism: Homo sapiens tissue_or_cell_type: Whole-person symptoms, serum and urine experimental_model: Historical controlled feeding study in six adult male volunteers; two diet-only deficient, two deficient plus antagonist, two supplemented controls limitations: Very small historical cohort; other vitamins and formula composition were controlled imperfectly. Diet-only and antagonist groups are distinguished. Measurements do not establish a universal symptom, adrenal disease mechanism or cellular CoA threshold. No full potassium balance study was done; the record does not establish B5-dependent renal potassium wasting or refractory potassium repletion. exposure: Tube-fed experimental formula; controls received pantothenic acid 20 mg/day, antagonist pair 750 then 1000 mg/day omega-methyl compound; recovery included 4000 mg/day vitamin. One man per pair received 10.8 mEq/day extra potassium. cross_nutrient: true evidence_location: Primary PDF pp.1643–1654; design, results and discussion. [b5-clin-hodges1958] Pantothenic acid deficiency in man. (1958). https://pubmed.ncbi.nlm.nih.gov/13587673/ DOI: 10.1172/jci103756

evidence_span

{"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"}

experimental_model

Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography

exposure

ATP/methionine reactions and PNPNP ligand complexes

limitations

Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.

nutrient_topic

Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus

organism

Human recombinant enzyme

plain_language

Potassium and magnesium had distinct contacts in the same phosphate-handling active site.

primary_references

[phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998

tissue_or_cell_type

Purified MAT2A active site

Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 672–683

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft

### phosphorus-mat-potassium The beta-phosphoryl oxygen of the MAT2A-bound PNPNP ligand contacted the essential potassium ion. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium and magnesium had distinct contacts in the same phosphate-handling active site. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998

cross_nutrient

Calcium-regulated channel activity -> local potassium signal.

experimental_model

Rat isolated arteries; potassium electrodes and blockers.

limitations

Pharmacology does not uniquely identify an SK/IK gene; not a dietary intervention.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rattus norvegicus

plain_language

Potassium can act locally as a signal between vessel cells.

primary_references

[k-edwards1998] K+ is an endothelium-derived hyperpolarizing factor in rat arteries (1998). https://pubmed.ncbi.nlm.nih.gov/9834033/ DOI: 10.1038/24388

tissue_or_cell_type

Arterial endothelium and myoendothelial space

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1580–1590

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat isolated arteries; potassium electrodes and blockers. · source_derived_draft · unverified_draft

### k-vascular-endothelial-release Acetylcholine produced a local potassium rise and hyperpolarization sensitive to combined calcium-activated potassium-channel blockers in rat arteries. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium can act locally as a signal between vessel cells. organism: Rattus norvegicus tissue_or_cell_type: Arterial endothelium and myoendothelial space experimental_model: Rat isolated arteries; potassium electrodes and blockers. limitations: Pharmacology does not uniquely identify an SK/IK gene; not a dietary intervention. cross_nutrient: Calcium-regulated channel activity -> local potassium signal. [k-edwards1998] K+ is an endothelium-derived hyperpolarizing factor in rat arteries (1998). https://pubmed.ncbi.nlm.nih.gov/9834033/ DOI: 10.1038/24388

experimental_model

Chemical formula KI; molar mass 166.0028 g/mol.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Equimolar ions have different masses and physiological handling.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

The potassium and iodide become separate ions.

primary_references

NIST Chemistry WebBook: potassium iodide · chemical reference · https://webbook.nist.gov/cgi/cbook.cgi?ID=7681110

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 40–46

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Chemical formula KI; molar mass 166.0028 g/mol. · source_derived_draft · unverified_draft

## ki-potassium The potassium and iodide become separate ions. A formula unit of potassium iodide supplies one potassium ion on dissolution. Model: Chemical formula KI; molar mass 166.0028 g/mol. Limitations: Equimolar ions have different masses and physiological handling. Evidence location: Primary abstract NIST Chemistry WebBook: potassium iodide · chemical reference · https://webbook.nist.gov/cgi/cbook.cgi?ID=7681110

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> sodium -> potassium

experimental_model

Dietary restriction in C57BL/6J mice with renal transport assays

limitations

Unchanged concentration does not imply absent mineralocorticoid action or exclude other ENaC regulators.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Mus musculus

plain_language

The potassium loss pattern did not require a measured rise in circulating aldosterone in this experiment.

primary_references

[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704

tissue_or_cell_type

Kidney distal nephron

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 191–201

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft

### combined-na-mg-restriction-aldosterone-not-elevated Plasma aldosterone in combined Na/Mg-restricted mice was not higher than with normal diet, although sodium restriction alone increased it. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The potassium loss pattern did not require a measured rise in circulating aldosterone in this experiment. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Unchanged concentration does not imply absent mineralocorticoid action or exclude other ENaC regulators. cross_nutrient: magnesium -> sodium -> potassium [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> sodium -> potassium

duration

Seven days

experimental_contrast

{"combination": "joint", "comparator": "Normal diet", "conditions": [{"entity_slug": "sodium", "state": "Restricted"}, {"entity_slug": "magnesium", "state": "Restricted"}], "effect_direction": "increase", "endpoint": "Native ROMK activity in DCT2/CNT", "intervention": "Combined dietary sodium and magnesium restriction"} Primary abstract PMID 41137719 / DOI 10.1113/JP287704 rechecked 2026-09-20. This comparison must not be separated into two single-deficiency effects.

experimental_model

Dietary restriction in C57BL/6J mice with renal transport assays

limitations

Co-occurrence supports the proposed mechanism; intracellular Mg and distal Na delivery were not directly measured.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Mus musculus

plain_language

In this combined shortage, the Mg-sensitive potassium pathway was more active while the sodium pathway that supports potassium exit remained available.

primary_references

[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704

tissue_or_cell_type

Kidney distal nephron

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 178–189

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft

### combined-na-mg-restriction-romk-hypokalemia Combined Na/Mg restriction increased native ROMK activity in DCT2/CNT and lowered plasma K, while ENaC cleavage markers were preserved relative to normal diet. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this combined shortage, the Mg-sensitive potassium pathway was more active while the sodium pathway that supports potassium exit remained available. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Co-occurrence supports the proposed mechanism; intracellular Mg and distal Na delivery were not directly measured. cross_nutrient: magnesium -> sodium -> potassium duration: Seven days [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704

cross_nutrient

magnesium -> potassium

experimental_model

Heterologous channel expression and patch-clamp

limitations

Excised-patch channel behavior does not quantify whole-body potassium loss in humans.

magnesium-pool

Extracellular free Mg2+

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Xenopus laevis host; mammalian ROMK channel

plain_language

Mg on the urine-facing side can also limit channel current; its action is separate from intracellular Mg.

primary_references

[yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617

tissue_or_cell_type

Oocyte membrane

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 141–152

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous channel expression and patch-clamp · source_derived_draft · unverified_draft

### mg-extracellular-romk2-block Extracellular Mg2+ also reduced ROMK2 single-channel current, with stronger apparent block as external K+ fell. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mg on the urine-facing side can also limit channel current; its action is separate from intracellular Mg. organism: Xenopus laevis host; mammalian ROMK channel tissue_or_cell_type: Oocyte membrane experimental_model: Heterologous channel expression and patch-clamp limitations: Excised-patch channel behavior does not quantify whole-body potassium loss in humans. cross_nutrient: magnesium -> potassium magnesium-pool: Extracellular free Mg2+ [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617

cross_nutrient

magnesium -> potassium

experimental_model

Whole-cell patch-clamp with controlled pipette Mg

limitations

Pipette-controlled Mg and voltage are not measurements of intracellular Mg during a human deficiency.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Rattus norvegicus

plain_language

Native kidney-cell recordings support the Mg brake on ROMK potassium flow seen in expressed channels.

primary_references

[yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617

tissue_or_cell_type

Cortical collecting-duct principal cells

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 129–139

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-cell patch-clamp with controlled pipette Mg · source_derived_draft · unverified_draft

### mg-native-ccd-romk-current-block Mg2+ supplied through the whole-cell pipette reduced tertiapin-Q-sensitive current in rat cortical collecting-duct principal cells. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Native kidney-cell recordings support the Mg brake on ROMK potassium flow seen in expressed channels. organism: Rattus norvegicus tissue_or_cell_type: Cortical collecting-duct principal cells experimental_model: Whole-cell patch-clamp with controlled pipette Mg limitations: Pipette-controlled Mg and voltage are not measurements of intracellular Mg during a human deficiency. cross_nutrient: magnesium -> potassium [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617

cross_nutrient

Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.

experimental_model

Phosphorylated pig-kidney Na/K-ATPase-ouabain complex crystallography.

limitations

Drug-stabilized inhibited state; it does not demonstrate physiological Mg transport.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Sus scrofa

plain_language

Magnesium can occupy a membrane ion site distinct from the ATP-associated catalytic site.

primary_references

[laursen-2013-nka] Crystal structure of the high-affinity Na+K+-ATPase-ouabain complex with Mg2+ bound in the cation binding site (2013). https://pubmed.ncbi.nlm.nih.gov/23776223/ DOI: 10.1073/pnas.1222308110

tissue_or_cell_type

Kidney enzyme crystals

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 845–855

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphorylated pig-kidney Na/K-ATPase-ouabain complex crystallography. · source_derived_draft · unverified_draft

### mg-nka-distinct-transport-site Mg occupied cation transport site II in the ouabain-bound E2P pig-kidney pump structure. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium can occupy a membrane ion site distinct from the ATP-associated catalytic site. organism: Sus scrofa tissue_or_cell_type: Kidney enzyme crystals experimental_model: Phosphorylated pig-kidney Na/K-ATPase-ouabain complex crystallography. limitations: Drug-stabilized inhibited state; it does not demonstrate physiological Mg transport. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [laursen-2013-nka] Crystal structure of the high-affinity Na+K+-ATPase-ouabain complex with Mg2+ bound in the cation binding site (2013). https://pubmed.ncbi.nlm.nih.gov/23776223/ DOI: 10.1073/pnas.1222308110

cross_nutrient

Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.

experimental_model

Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP.

limitations

Measured stoichiometry applies to specified ionic conditions; no Mg titration was performed.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

ATP turnover was directly linked to outward sodium pumping in a magnesium-containing preparation.

primary_references

[garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297

tissue_or_cell_type

Resealed erythrocyte ghosts

transport_direction

Sodium: intracellular ghost compartment to external medium.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 819–830

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. · source_derived_draft · unverified_draft

### mg-nka-isotope-atp-sodium-coupling In Mg-loaded human red-cell ghosts, ouabain-sensitive hydrolysis of one ATP accompanied loss of about three sodium ions. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP turnover was directly linked to outward sodium pumping in a magnesium-containing preparation. organism: Homo sapiens tissue_or_cell_type: Resealed erythrocyte ghosts experimental_model: Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. limitations: Measured stoichiometry applies to specified ionic conditions; no Mg titration was performed. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. transport_direction: Sodium: intracellular ghost compartment to external medium. [garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297

cross_nutrient

Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.

experimental_model

Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP.

limitations

This experiment found unequal fluxes but did not itself measure an exact 3:2 ratio.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

The pump moves the two nutrient ions in opposite directions.

primary_references

[garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297

tissue_or_cell_type

Erythrocytes

transport_direction

Sodium outward; potassium inward.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 832–843

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. · source_derived_draft · unverified_draft

### mg-nka-isotope-opposed-flux Sodium-24 and potassium-42 experiments demonstrated ouabain-sensitive sodium efflux and potassium influx in human red cells. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pump moves the two nutrient ions in opposite directions. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. limitations: This experiment found unequal fluxes but did not itself measure an exact 3:2 ratio. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. transport_direction: Sodium outward; potassium inward. [garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> sodium -> potassium

experimental_model

Dietary restriction in C57BL/6J mice with renal transport assays

limitations

Integrated mechanism supported across experiments; enhanced distal Na delivery was not demonstrated and is not required by these data.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Mus musculus

plain_language

Sodium entry changes the electrical conditions for potassium exit; lifting the Mg brake on ROMK matters when that driving force is available.

primary_references

[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704 [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617

spatial_transport_direction

Na+: tubular lumen to cell via ENaC; K+: cell to lumen via ROMK.

tissue_or_cell_type

Kidney distal nephron

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 203–215

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft

### mg-romk-enac-conditional-k-secretory-chain The mouse findings support a model in which sustained ENaC sodium entry and higher ROMK conductance jointly favor potassium secretion during combined Na/Mg restriction. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium entry changes the electrical conditions for potassium exit; lifting the Mg brake on ROMK matters when that driving force is available. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Integrated mechanism supported across experiments; enhanced distal Na delivery was not demonstrated and is not required by these data. cross_nutrient: magnesium -> sodium -> potassium spatial_transport_direction: Na+: tubular lumen to cell via ENaC; K+: cell to lumen via ROMK. [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704 [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617

cross_nutrient

magnesium -> potassium

experimental_model

Heterologous channel expression and patch-clamp

limitations

Excised-patch channel behavior does not quantify whole-body potassium loss in humans.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Xenopus laevis host; mammalian ROMK channel

plain_language

Mg inside the cell can obstruct outward potassium flow through ROMK; this is a conduction effect, not evidence that the channel disappears.

primary_references

[nichols-1994-romk1] Mg(2+)-dependent inward rectification of ROMK1 potassium channels expressed in Xenopus oocytes (1994). https://pubmed.ncbi.nlm.nih.gov/8057249/ DOI: 10.1113/jphysiol.1994.sp020141

tissue_or_cell_type

Oocyte membrane

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 104–114

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous channel expression and patch-clamp · source_derived_draft · unverified_draft

### mg-romk1-outward-current-block Cytoplasmic Mg2+ caused voltage-dependent reduction of ROMK1 outward single-channel current without reducing channel open probability. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mg inside the cell can obstruct outward potassium flow through ROMK; this is a conduction effect, not evidence that the channel disappears. organism: Xenopus laevis host; mammalian ROMK channel tissue_or_cell_type: Oocyte membrane experimental_model: Heterologous channel expression and patch-clamp limitations: Excised-patch channel behavior does not quantify whole-body potassium loss in humans. cross_nutrient: magnesium -> potassium [nichols-1994-romk1] Mg(2+)-dependent inward rectification of ROMK1 potassium channels expressed in Xenopus oocytes (1994). https://pubmed.ncbi.nlm.nih.gov/8057249/ DOI: 10.1113/jphysiol.1994.sp020141

evidence_access

Primary abstract

experimental_model

Rat BRIN-BD11 culture, washout and rechallenge experiments.

limitations

Exposure concentration/duration before washout are not resolved in the accessed abstract; no human chronic-use threshold is inferred.

nutrient_topic

L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine

plain_language

A strong acute response need not persist after prolonged exposure.

primary_references

Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 400–406

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat BRIN-BD11 culture, washout and rechallenge experiments. · source_derived_draft · unverified_draft

## alanine-beta-chronic-desensitization A strong acute response need not persist after prolonged exposure. Prolonged alanine culture reduced subsequent acute alanine-stimulated insulin secretion by 74%, without reducing responses to glucose, KCl or ketoisocaproate; 18 hours without alanine partly restored responsiveness. Model: Rat BRIN-BD11 culture, washout and rechallenge experiments. Limitations: Exposure concentration/duration before washout are not resolved in the accessed abstract; no human chronic-use threshold is inferred. Evidence access: Primary abstract Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138

evidence_span

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experimental_model

Simultaneous isotope-dilution and serum measurements, including serial observations

exposure

Observed variation in body composition

limitations

Historical observational regression; serum-water sodium and exchangeable pools are not interchangeable with current clinical plasma measurements or all body sodium. Not an individual correction calculator.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Human patients with chronic illnesses

plain_language

Blood sodium reflects a relationship between body cations and water, rather than a simple count of how much sodium was eaten.

primary_references

[sodium-p13575523] Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. (1958). https://pubmed.ncbi.nlm.nih.gov/13575523/ DOI: 10.1172/jci103712

tissue_or_cell_type

Whole-body water and exchangeable cations

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 265–276

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Simultaneous isotope-dilution and serum measurements, including serial observations · source_derived_draft · unverified_draft

### sodium-body-water-ratio Serum-water sodium correlated strongly with (exchangeable sodium + exchangeable potassium)/total body water in the studied patients. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood sodium reflects a relationship between body cations and water, rather than a simple count of how much sodium was eaten. organism: Human patients with chronic illnesses tissue_or_cell_type: Whole-body water and exchangeable cations experimental_model: Simultaneous isotope-dilution and serum measurements, including serial observations limitations: Historical observational regression; serum-water sodium and exchangeable pools are not interchangeable with current clinical plasma measurements or all body sodium. Not an individual correction calculator. exposure: Observed variation in body composition evidence_span: {"source_cache": "artifacts/sodium-research/13575523.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee58d9f6c640fec095876c15e7ddf6fe8bf539cb972c74841db02d2640eebbe2", "start_char": 54337, "end_char": 56036, "text_sha256": "29b3a155f7b33a8b86aa9e30182063d71f5af3c60910a237794c1310094a4c39"} [sodium-p13575523] Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. (1958). https://pubmed.ncbi.nlm.nih.gov/13575523/ DOI: 10.1172/jci103712

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/8589714.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c85f54f2086e1dc34cabaa8e4521a157bfeb5512b7882ca214ddfa2597b9bc4e", "start_char": 0, "end_char": 696, "text_sha256": "c85f54f2086e1dc34cabaa8e4521a157bfeb5512b7882ca214ddfa2597b9bc4e"}

experimental_model

Human family genetics and sodium-channel functional testing

exposure

Loss-of-function alpha- or beta-subunit variants in five kindreds

limitations

Autosomal recessive pseudohypoaldosteronism; not ordinary dietary sodium deficiency and not proof that additional aldosterone can repair the channel.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Human

plain_language

Sodium-channel failure can impair the normal balance of potassium and acid as well as sodium.

primary_references

[sodium-p8589714] Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. (1996). https://pubmed.ncbi.nlm.nih.gov/8589714/ DOI: 10.1038/ng0396-248

tissue_or_cell_type

ENaC-dependent epithelia and systemic electrolyte phenotype

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 941–952

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human family genetics and sodium-channel functional testing · source_derived_draft · unverified_draft

### sodium-enac-loss-potassium Affected individuals had salt wasting with hyperkalemia and acidosis despite mineralocorticoid unresponsiveness. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium-channel failure can impair the normal balance of potassium and acid as well as sodium. organism: Human tissue_or_cell_type: ENaC-dependent epithelia and systemic electrolyte phenotype experimental_model: Human family genetics and sodium-channel functional testing limitations: Autosomal recessive pseudohypoaldosteronism; not ordinary dietary sodium deficiency and not proof that additional aldosterone can repair the channel. exposure: Loss-of-function alpha- or beta-subunit variants in five kindreds evidence_span: {"source_cache": "artifacts/sodium-research/8589714.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c85f54f2086e1dc34cabaa8e4521a157bfeb5512b7882ca214ddfa2597b9bc4e", "start_char": 0, "end_char": 696, "text_sha256": "c85f54f2086e1dc34cabaa8e4521a157bfeb5512b7882ca214ddfa2597b9bc4e"} [sodium-p8589714] Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. (1996). https://pubmed.ncbi.nlm.nih.gov/8589714/ DOI: 10.1038/ng0396-248

evidence_span

{"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"}

experimental_model

Whole-cell current reversal measurements

exposure

Ion substitution, intracellular sodium/glutamate and extracellular potassium

limitations

Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Mammalian GLT-1 expressed in Chinese hamster ovary cells

plain_language

Glutamate clearance uses sodium, potassium and proton gradients together.

primary_references

[sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998

tissue_or_cell_type

Plasma membrane

transport_effect

raises Uptake of one glutamate anion with three sodium ions and one proton.

transport_pool

the expressing cell Uptake of one glutamate anion with three sodium ions and one proton.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 369–380

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-cell current reversal measurements · source_derived_draft · unverified_draft

### sodium-glt1-stoichiometry Current reversal measurements supported uptake of one glutamate anion with three sodium ions and one proton, coupled to outward movement of one potassium ion. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutamate clearance uses sodium, potassium and proton gradients together. organism: Mammalian GLT-1 expressed in Chinese hamster ovary cells tissue_or_cell_type: Plasma membrane experimental_model: Whole-cell current reversal measurements limitations: Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result. exposure: Ion substitution, intracellular sodium/glutamate and extracellular potassium evidence_span: {"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"} [sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998

evidence_access

Primary abstract

experimental_model

Dog kidney enzyme binding assay.

limitations

No human dietary sodium recommendation follows.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

The ionic environment changes how vanadate interacts with the pump.

primary_references

Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 246–252

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Dog kidney enzyme binding assay. · source_derived_draft · unverified_draft

## vanadium-pump-sodium The ionic environment changes how vanadate interacts with the pump. Sodium decreased vanadate binding in magnesium-containing medium, whereas sodium and potassium had little effect in the manganese condition. Model: Dog kidney enzyme binding assay. Limitations: No human dietary sodium recommendation follows. Evidence access: Primary abstract Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B1 shortage -> renal electrolyte handling in case evidence.

experimental_model

Two pediatric cases.

exposure

Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.

limitations

The authors attributed the pattern to renal losses; individual electrolyte fluxes and transporter mediators are not established here.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

B1 shortage may accompany kidney losses, which differ from minerals simply moving into cells.

primary_references

[b1-maiorana2014] Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis (2014). https://pubmed.ncbi.nlm.nih.gov/24985016/ DOI: 10.1016/j.nut.2014.02.019

tissue_or_cell_type

Kidney and blood

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1758–1769

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two pediatric cases. · source_derived_draft · unverified_draft

### b1-deficiency-renal-electrolyte-loss Two leukemia cases with acute thiamine deficiency showed proximal tubular dysfunction and electrolyte abnormalities resembling refeeding syndrome. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 shortage may accompany kidney losses, which differ from minerals simply moving into cells. organism: Homo sapiens tissue_or_cell_type: Kidney and blood experimental_model: Two pediatric cases. limitations: The authors attributed the pattern to renal losses; individual electrolyte fluxes and transporter mediators are not established here. cross_nutrient: B1 shortage -> renal electrolyte handling in case evidence. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-maiorana2014] Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis (2014). https://pubmed.ncbi.nlm.nih.gov/24985016/ DOI: 10.1016/j.nut.2014.02.019

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B1 repletion and K/P/Mg management address different requirements.

experimental_model

Prospective cohort and individual case histories.

exposure

Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.

limitations

No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Providing vitamins did not by itself prevent every electrolyte and fluid complication.

primary_references

[b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173

tissue_or_cell_type

Whole-body clinical nutrition

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1733–1744

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective cohort and individual case histories. · source_derived_draft · unverified_draft

### b1-refeeding-vitamins-not-complete-rescue Refeeding syndrome occurred in three cohort participants; two had received vitamin B/C preparations before nutrition support. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing vitamins did not by itself prevent every electrolyte and fluid complication. organism: Homo sapiens tissue_or_cell_type: Whole-body clinical nutrition experimental_model: Prospective cohort and individual case histories. limitations: No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency. cross_nutrient: B1 repletion and K/P/Mg management address different requirements. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Links thiamine-dependent carbon metabolism with synthesis of a choline-containing transmitter; no choline repletion outcome was tested.

evidence_location

Abstract

evidence_span

declined by 50 and 75%, respectively

experimental_model

Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm.

exposure

Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices

limitations

This tracer experiment did not test choline deficiency or choline supplementation; synthesis labeling is not transmitter release.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

Thiamine disruption limited stimulated production of the choline-containing transmitter from glucose-derived carbon.

primary_references

[gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667

tissue_or_cell_type

Brain slices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1112–1125

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. · source_derived_draft · unverified_draft

### thiamine-def-stimulated-acetylcholine-synthesis The potassium-induced increment in glucose-derived carbon-14 acetylcholine was 75% lower in deficient rat brain slices. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Thiamine disruption limited stimulated production of the choline-containing transmitter from glucose-derived carbon. organism: Rattus norvegicus tissue_or_cell_type: Brain slices experimental_model: Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. limitations: This tracer experiment did not test choline deficiency or choline supplementation; synthesis labeling is not transmitter release. evidence_location: Abstract evidence_span: declined by 50 and 75%, respectively cross_nutrient: Links thiamine-dependent carbon metabolism with synthesis of a choline-containing transmitter; no choline repletion outcome was tested. exposure: Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices [gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Abstract

evidence_span

under resting conditions

experimental_model

Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm.

exposure

Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices

limitations

Carbon dioxide labeling measures glucose oxidation under this stimulation protocol, not whole-brain ATP directly. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

The slices could maintain resting oxidation but had less capacity to increase it when stimulated.

primary_references

[gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667

tissue_or_cell_type

Brain slices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1098–1110

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. · source_derived_draft · unverified_draft

### thiamine-def-stimulated-glucose-oxidation The potassium-induced increment in carbon-14 carbon dioxide production from labeled glucose was 50% lower in deficient rat brain slices; resting production was similar to controls. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The slices could maintain resting oxidation but had less capacity to increase it when stimulated. organism: Rattus norvegicus tissue_or_cell_type: Brain slices experimental_model: Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. limitations: Carbon dioxide labeling measures glucose oxidation under this stimulation protocol, not whole-brain ATP directly. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold. evidence_location: Abstract evidence_span: under resting conditions exposure: Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices [gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/9326936.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e", "start_char": 0, "end_char": 1227, "text_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e"}

experimental_model

Genetics in seventeen kindreds

exposure

Loss-of-function CLCNKB variants

limitations

This cohort had normal magnesium and variable calciuria; do not universalize the full phenotype.

nutrient_topic

Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride

organism

Human

plain_language

A chloride-channel defect can drive loss of other electrolytes.

primary_references

[chloride-p9326936] Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. (1997). https://pubmed.ncbi.nlm.nih.gov/9326936/ DOI: 10.1038/ng1097-171

tissue_or_cell_type

Renal salt handling

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 887–898

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetics in seventeen kindreds · source_derived_draft · unverified_draft

### chloride-clcnkb-salt CLCNKB loss-of-function variants caused renal salt-wasting hypokalemic alkalosis in the studied families. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A chloride-channel defect can drive loss of other electrolytes. organism: Human tissue_or_cell_type: Renal salt handling experimental_model: Genetics in seventeen kindreds limitations: This cohort had normal magnesium and variable calciuria; do not universalize the full phenotype. exposure: Loss-of-function CLCNKB variants evidence_span: {"source_cache": "artifacts/chloride-research/9326936.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e", "start_char": 0, "end_char": 1227, "text_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e"} [chloride-p9326936] Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. (1997). https://pubmed.ncbi.nlm.nih.gov/9326936/ DOI: 10.1038/ng1097-171

evidence_span

{"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"}

experimental_model

Developmental expression and antisense suppression

exposure

KCC2 expression during maturation; antisense inhibition

limitations

Neuronal gradient mechanism; dietary chloride restriction is not the intervention.

nutrient_topic

Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride

organism

Rat

plain_language

Potassium-coupled chloride removal helps mature neurons respond to GABA with inhibition.

primary_references

[chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697

tissue_or_cell_type

Hippocampal pyramidal neurons

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 393–404

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Developmental expression and antisense suppression · source_derived_draft · unverified_draft

### chloride-kcc2-cl-extrusion Developmental KCC2 expression accompanied the shift toward hyperpolarizing GABA-A responses. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium-coupled chloride removal helps mature neurons respond to GABA with inhibition. organism: Rat tissue_or_cell_type: Hippocampal pyramidal neurons experimental_model: Developmental expression and antisense suppression limitations: Neuronal gradient mechanism; dietary chloride restriction is not the intervention. exposure: KCC2 expression during maturation; antisense inhibition evidence_span: {"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"} [chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697

evidence_span

{"source_cache": "artifacts/chloride-research/2012204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac", "start_char": 0, "end_char": 1695, "text_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac"}

experimental_model

Perfused isolated juxtaglomerular apparatus

exposure

Luminal ion substitutions and 1 µM bumetanide

limitations

Pharmacological evidence for macula-densa Na-K-2Cl transport; molecular NKCC2 was not genetically tested in this experiment.

nutrient_topic

Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride

organism

Rabbit

plain_language

The chloride must engage the transport system to produce the usual signal.

primary_references

[chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486

tissue_or_cell_type

Macula densa and renin-secreting apparatus

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 575–586

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused isolated juxtaglomerular apparatus · source_derived_draft · unverified_draft

### chloride-macula-transport-renin Luminal bumetanide increased renin release during high-NaCl perfusion, supporting cotransporter-dependent sensing. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chloride must engage the transport system to produce the usual signal. organism: Rabbit tissue_or_cell_type: Macula densa and renin-secreting apparatus experimental_model: Perfused isolated juxtaglomerular apparatus limitations: Pharmacological evidence for macula-densa Na-K-2Cl transport; molecular NKCC2 was not genetically tested in this experiment. exposure: Luminal ion substitutions and 1 µM bumetanide evidence_span: {"source_cache": "artifacts/chloride-research/2012204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac", "start_char": 0, "end_char": 1695, "text_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac"} [chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486

evidence_span

{"source_cache": "artifacts/chloride-research/19295148.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f", "start_char": 0, "end_char": 982, "text_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f"}

experimental_model

Nkcc1 knockout and neuronal activity measurements

exposure

Nkcc1 deletion

limitations

Developmental hippocampal model; does not generalize to every immature neuron.

nutrient_topic

Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride

organism

Mouse

plain_language

Chloride loading can help GABA excite developing neurons in this specific circuit.

primary_references

[chloride-p19295148] NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. (2009). https://pubmed.ncbi.nlm.nih.gov/19295148/ DOI: 10.1523/jneurosci.1377-08.2009

tissue_or_cell_type

Early postnatal hippocampal CA1 network

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 419–430

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nkcc1 knockout and neuronal activity measurements · source_derived_draft · unverified_draft

### chloride-nkcc1-gaba Nkcc1 deletion attenuated GABA-triggered depolarization and calcium transients during early hippocampal development. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride loading can help GABA excite developing neurons in this specific circuit. organism: Mouse tissue_or_cell_type: Early postnatal hippocampal CA1 network experimental_model: Nkcc1 knockout and neuronal activity measurements limitations: Developmental hippocampal model; does not generalize to every immature neuron. exposure: Nkcc1 deletion evidence_span: {"source_cache": "artifacts/chloride-research/19295148.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f", "start_char": 0, "end_char": 982, "text_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f"} [chloride-p19295148] NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. (2009). https://pubmed.ncbi.nlm.nih.gov/19295148/ DOI: 10.1523/jneurosci.1377-08.2009

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/2450456.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7", "start_char": 0, "end_char": 1348, "text_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7"}

experimental_model

Human depletion–repletion balance experiment

exposure

Furosemide plus restricted NaCl; oral KCl repletion over 36 hours

limitations

Loss-associated depletion; KCl supplies potassium too. Mechanism does not imply self-treatment or apply to every alkalosis.

nutrient_topic

Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride

organism

Human men

plain_language

Restoring volume was not necessary for correction in this experiment.

primary_references

[chloride-p2450456] On the mechanism by which chloride corrects metabolic alkalosis in man. (1988). https://pubmed.ncbi.nlm.nih.gov/2450456/ DOI: 10.1016/0002-9343(88)90265-3

tissue_or_cell_type

Kidney and systemic acid–base balance

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 835–846

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human depletion–repletion balance experiment · source_derived_draft · unverified_draft

### chloride-repletion-alkalosis Oral KCl corrected induced chloride-depletion alkalosis while plasma volume, body weight and filtration remained reduced. Condition category: nutrient_deficiency nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring volume was not necessary for correction in this experiment. organism: Human men tissue_or_cell_type: Kidney and systemic acid–base balance experimental_model: Human depletion–repletion balance experiment limitations: Loss-associated depletion; KCl supplies potassium too. Mechanism does not imply self-treatment or apply to every alkalosis. exposure: Furosemide plus restricted NaCl; oral KCl repletion over 36 hours evidence_span: {"source_cache": "artifacts/chloride-research/2450456.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7", "start_char": 0, "end_char": 1348, "text_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7"} [chloride-p2450456] On the mechanism by which chloride corrects metabolic alkalosis in man. (1988). https://pubmed.ncbi.nlm.nih.gov/2450456/ DOI: 10.1016/0002-9343(88)90265-3

evidence_access

Primary full text

experimental_model

Male C57BL/6J mice aged four to six weeks; slice patch clamp with synaptic blockers.

limitations

Authors attributed the response to GPR158; pharmacology alone is weaker than a receptor-knockout test and does not prove direct channel binding.

nutrient_topic

Glycine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Glycine

plain_language

Glycine-sensitive signaling intersects with potassium-channel control of firing.

primary_references

Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38884814/ · DOI 10.1007/s00018-024-05260-w

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 258–264

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Male C57BL/6J mice aged four to six weeks; slice patch clamp with synaptic blockers. · source_derived_draft · unverified_draft

## glycine-gpr158-potassium-current Glycine-sensitive signaling intersects with potassium-channel control of firing. In mouse accumbens slices, 1 mM glycine increased medium-spiny-neuron firing and reduced M-current amplitude; a selective M-current inhibitor mimicked and occluded the response. Model: Male C57BL/6J mice aged four to six weeks; slice patch clamp with synaptic blockers. Limitations: Authors attributed the response to GPR158; pharmacology alone is weaker than a receptor-knockout test and does not prove direct channel binding. Evidence access: Primary full text Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38884814/ · DOI 10.1007/s00018-024-05260-w

availability_state

nutrient_deficiency Imported condition classification; unverified.

endpoint

Luminal omeprazole abolished active net potassium absorption in the same potassium-restricted rabbit collecting-duct preparation.

experimental-exposure

Microperfused inner-stripe outer medullary collecting ducts from rabbits fed 0.55% potassium diet for 7-14 days; luminal omeprazole 0.1 mM.

experimental_model

Microperfused inner-stripe outer medullary collecting ducts from rabbits fed 0.55% potassium diet for 7-14 days; luminal omeprazole 0.1 mM.

limitations

Pharmacological activity assignment; the experiment does not isolate ATP4A versus ATP12A. Total-CO2 flux is an acidification surrogate.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Oryctolagus cuniculus

plain_language

The proton-pump-compatible activity also recovered potassium from tubular fluid.

primary_references

[wingo-1989-hka] Active proton secretion and potassium absorption in the rabbit outer medullary collecting duct. Functional evidence for proton-potassium-activated adenosine triphosphatase (1989). https://pubmed.ncbi.nlm.nih.gov/2544629/ DOI: 10.1172/JCI114165

tissue_or_cell_type

inner-stripe outer medullary collecting duct

transport_direction

potassium: tubular lumen toward blood; protons: cell toward tubular lumen

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1110–1122

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microperfused inner-stripe outer medullary collecting ducts from rabbits fed 0.55% potassium diet for 7-14 days; luminal omeprazole 0.1 mM. · source_derived_draft · unverified_draft

### hka-sensitive-potassium-absorption Luminal omeprazole abolished active net potassium absorption in the same potassium-restricted rabbit collecting-duct preparation. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The proton-pump-compatible activity also recovered potassium from tubular fluid. organism: Oryctolagus cuniculus tissue_or_cell_type: inner-stripe outer medullary collecting duct experimental_model: Microperfused inner-stripe outer medullary collecting ducts from rabbits fed 0.55% potassium diet for 7-14 days; luminal omeprazole 0.1 mM. limitations: Pharmacological activity assignment; the experiment does not isolate ATP4A versus ATP12A. Total-CO2 flux is an acidification surrogate. transport_direction: potassium: tubular lumen toward blood; protons: cell toward tubular lumen experimental-exposure: Microperfused inner-stripe outer medullary collecting ducts from rabbits fed 0.55% potassium diet for 7-14 days; luminal omeprazole 0.1 mM. endpoint: Luminal omeprazole abolished active net potassium absorption in the same potassium-restricted rabbit collecting-duct preparation. [wingo-1989-hka] Active proton secretion and potassium absorption in the rabbit outer medullary collecting duct. Functional evidence for proton-potassium-activated adenosine triphosphatase (1989). https://pubmed.ncbi.nlm.nih.gov/2544629/ DOI: 10.1172/JCI114165

cross_nutrient

Free ATP must be distinguished from its magnesium complex.

experimental_model

Rat beta-cell inside-out patches.

limitations

Excised patches do not reproduce all intact-cell metabolic regulation.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rat

plain_language

ATP can close the potassium channel through nucleotide regulation.

primary_references

[ashcroft-1989-magnesium] ATP-sensitive K+ channels in rat pancreatic beta-cells: modulation by ATP and Mg2+ ions (1989). https://pmc.ncbi.nlm.nih.gov/articles/PMC1189219/ DOI: 10.1113/jphysiol.1989.sp017765

tissue_or_cell_type

Pancreatic beta-cell membrane

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 786–796

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat beta-cell inside-out patches. · source_derived_draft · unverified_draft

### k-beta-atp-inhibition Free ATP and nonhydrolyzable ATP analogues inhibited beta-cell KATP channels without requiring phosphorylation. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP can close the potassium channel through nucleotide regulation. organism: Rat tissue_or_cell_type: Pancreatic beta-cell membrane experimental_model: Rat beta-cell inside-out patches. limitations: Excised patches do not reproduce all intact-cell metabolic regulation. cross_nutrient: Free ATP must be distinguished from its magnesium complex. [ashcroft-1989-magnesium] ATP-sensitive K+ channels in rat pancreatic beta-cells: modulation by ATP and Mg2+ ions (1989). https://pmc.ncbi.nlm.nih.gov/articles/PMC1189219/ DOI: 10.1113/jphysiol.1989.sp017765

experimental_model

Uncontrolled run-in; CKD G3b-4.

exposure

40 mmol/day KCl; 83% used RAAS inhibitors.

limitations

11% is this cohort rate, not general-population risk or a dose recommendation.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

Reduced kidney clearance changes the response to an added potassium load.

primary_references

[k-gritter2022] Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD (2022). https://pubmed.ncbi.nlm.nih.gov/35609996/ DOI: 10.1681/asn.2022020147

tissue_or_cell_type

Plasma

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1638–1648

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Uncontrolled run-in; CKD G3b-4. · source_derived_draft · unverified_draft

### k-ckd-kcl-plasma-rise Two weeks of KCl raised mean plasma potassium from 4.3 to 4.7 mmol/L; 21 of 191 CKD participants developed hyperkalemia. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced kidney clearance changes the response to an added potassium load. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Uncontrolled run-in; CKD G3b-4. limitations: 11% is this cohort rate, not general-population risk or a dose recommendation. exposure: 40 mmol/day KCl; 83% used RAAS inhibitors. [k-gritter2022] Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD (2022). https://pubmed.ncbi.nlm.nih.gov/35609996/ DOI: 10.1681/asn.2022020147

availability_state

nutrient_deficiency Imported condition classification; unverified.

endpoint

Potassium depletion increased collecting-tubule potassium-stimulated, ouabain-insensitive ATPase activity in rats.

experimental-exposure

Microdissected rabbit nephron segments and collecting tubules of potassium-depleted rats.

experimental_model

Microdissected rabbit nephron segments and collecting tubules of potassium-depleted rats.

limitations

ATP hydrolysis and inhibitor sensitivity establish activity class, not a specific protein isoform or whole-animal flux.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rattus norvegicus

plain_language

The distal kidney increased an ATP-consuming activity compatible with potassium recovery.

primary_references

[doucet-1987-hka] Characterization of K-ATPase activity in distal nephron: stimulation by potassium depletion (1987). https://pubmed.ncbi.nlm.nih.gov/2957926/ DOI: 10.1152/ajprenal.1987.253.3.F418

tissue_or_cell_type

collecting tubule

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1124–1135

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microdissected rabbit nephron segments and collecting tubules of potassium-depleted rats. · source_derived_draft · unverified_draft

### k-depletion-increases-hka-activity Potassium depletion increased collecting-tubule potassium-stimulated, ouabain-insensitive ATPase activity in rats. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The distal kidney increased an ATP-consuming activity compatible with potassium recovery. organism: Rattus norvegicus tissue_or_cell_type: collecting tubule experimental_model: Microdissected rabbit nephron segments and collecting tubules of potassium-depleted rats. limitations: ATP hydrolysis and inhibitor sensitivity establish activity class, not a specific protein isoform or whole-animal flux. experimental-exposure: Microdissected rabbit nephron segments and collecting tubules of potassium-depleted rats. endpoint: Potassium depletion increased collecting-tubule potassium-stimulated, ouabain-insensitive ATPase activity in rats. [doucet-1987-hka] Characterization of K-ATPase activity in distal nephron: stimulation by potassium depletion (1987). https://pubmed.ncbi.nlm.nih.gov/2957926/ DOI: 10.1152/ajprenal.1987.253.3.F418

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium status alters machinery that also controls sodium transport.

experimental_model

Rat/mouse soleus and extensor digitorum longus; K-free diet, diuretic or K-binding-resin depletion models.

limitations

Diet, diuretic and resin models differ; abstract does not provide each regimen duration.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rat and mouse

plain_language

Depleted muscle had fewer functional sodium-potassium pumps.

primary_references

[norgaard-1981-muscle] Potassium depletion decreases the number of 3H-ouabain binding sites and the active Na-K transport in skeletal muscle (1981). https://www.nature.com/articles/293739a0 DOI: 10.1038/293739a0

tissue_or_cell_type

Soleus/extensor digitorum longus

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 739–749

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat/mouse soleus and extensor digitorum longus; K-free diet, diuretic or K-binding-resin depletion models. · source_derived_draft · unverified_draft

### k-depletion-muscle-pump-loss Rodent potassium depletion reversibly reduced muscle ouabain-binding sites and pump-mediated potassium uptake capacity. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Depleted muscle had fewer functional sodium-potassium pumps. organism: Rat and mouse tissue_or_cell_type: Soleus/extensor digitorum longus experimental_model: Rat/mouse soleus and extensor digitorum longus; K-free diet, diuretic or K-binding-resin depletion models. limitations: Diet, diuretic and resin models differ; abstract does not provide each regimen duration. cross_nutrient: Potassium status alters machinery that also controls sodium transport. [norgaard-1981-muscle] Potassium depletion decreases the number of 3H-ouabain binding sites and the active Na-K transport in skeletal muscle (1981). https://www.nature.com/articles/293739a0 DOI: 10.1038/293739a0

experimental_model

Mouse macrophages with Nek7 deletion/reconstitution; ATP, nigericin or gramicidin; high-K control, interaction assays.

limitations

NEK7 catalytic activity was dispensable; this is not proof of potassium binding directly to NEK7.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mouse

plain_language

Potassium loss signals through an assembly protein before caspase activation.

primary_references

[he-2016-nek7] NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4810788/ DOI: 10.1038/nature16959

tissue_or_cell_type

Bone-marrow macrophages

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 880–889

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse macrophages with Nek7 deletion/reconstitution; ATP, nigericin or gramicidin; high-K control, interaction assays. · source_derived_draft · unverified_draft

### k-efflux-nek7-assembly NEK7 loss blocked inflammasome assembly downstream of preserved K efflux; 50 mM KCl prevented the induced NEK7-NLRP3 interaction. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium loss signals through an assembly protein before caspase activation. organism: Mouse tissue_or_cell_type: Bone-marrow macrophages experimental_model: Mouse macrophages with Nek7 deletion/reconstitution; ATP, nigericin or gramicidin; high-K control, interaction assays. limitations: NEK7 catalytic activity was dispensable; this is not proof of potassium binding directly to NEK7. [he-2016-nek7] NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4810788/ DOI: 10.1038/nature16959

experimental_model

Rectal dialysis with 5 mmol/L barium.

limitations

Barium is not BK-specific; combine this with expression evidence without asserting exclusive BK mediation.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

Part of the extra gut potassium loss depended on a blocker-sensitive pathway.

primary_references

[k-sandle2005] Enhanced large intestinal potassium permeability in end-stage renal disease (2005). https://pubmed.ncbi.nlm.nih.gov/15772943/ DOI: 10.1002/path.1750

tissue_or_cell_type

Human rectum

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1487–1496

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rectal dialysis with 5 mmol/L barium. · source_derived_draft · unverified_draft

### k-esrd-colonic-barium-sensitive-secretion Luminal barium reduced potassium secretion by about 45% in the kidney-failure group, supporting a potassium-channel contribution. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Part of the extra gut potassium loss depended on a blocker-sensitive pathway. organism: Homo sapiens tissue_or_cell_type: Human rectum experimental_model: Rectal dialysis with 5 mmol/L barium. limitations: Barium is not BK-specific; combine this with expression evidence without asserting exclusive BK mediation. [k-sandle2005] Enhanced large intestinal potassium permeability in end-stage renal disease (2005). https://pubmed.ncbi.nlm.nih.gov/15772943/ DOI: 10.1002/path.1750

cross_nutrient

Kidney failure -> extra-renal potassium handling.

experimental_model

Small human biopsy and rectal-dialysis groups.

limitations

Expression plus association does not identify every flux pathway; no diet intervention.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

The colon can increase its potassium-disposal role when kidney function is severely reduced.

primary_references

[k-sandle2005] Enhanced large intestinal potassium permeability in end-stage renal disease (2005). https://pubmed.ncbi.nlm.nih.gov/15772943/ DOI: 10.1002/path.1750

tissue_or_cell_type

Human distal colon and rectum

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1475–1485

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small human biopsy and rectal-dialysis groups. · source_derived_draft · unverified_draft

### k-esrd-colonic-bk-upregulation Patients with end-stage renal disease showed higher colonic BK expression and approximately threefold higher rectal potassium secretion than controls. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The colon can increase its potassium-disposal role when kidney function is severely reduced. organism: Homo sapiens tissue_or_cell_type: Human distal colon and rectum experimental_model: Small human biopsy and rectal-dialysis groups. limitations: Expression plus association does not identify every flux pathway; no diet intervention. cross_nutrient: Kidney failure -> extra-renal potassium handling. [k-sandle2005] Enhanced large intestinal potassium permeability in end-stage renal disease (2005). https://pubmed.ncbi.nlm.nih.gov/15772943/ DOI: 10.1002/path.1750

cross_nutrient

Carbohydrate metabolism regulates a potassium conductance rather than proving potassium supplementation benefit.

experimental_model

Cell-attached patch recordings in isolated rat pancreatic beta cells; glucose and metabolism perturbation.

limitations

The experiment does not establish dietary potassium control of insulin secretion.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rat

plain_language

The glucose fuel signal reduced potassium conductance.

primary_references

[ashcroft-1984-glucose] Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells (1984). https://www.nature.com/articles/312446a0 DOI: 10.1038/312446a0

tissue_or_cell_type

Pancreatic beta cells

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 774–784

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-attached patch recordings in isolated rat pancreatic beta cells; glucose and metabolism perturbation. · source_derived_draft · unverified_draft

### k-glucose-closes-beta-channel Glucose metabolism closed resting potassium channels in cell-attached rat beta-cell recordings. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The glucose fuel signal reduced potassium conductance. organism: Rat tissue_or_cell_type: Pancreatic beta cells experimental_model: Cell-attached patch recordings in isolated rat pancreatic beta cells; glucose and metabolism perturbation. limitations: The experiment does not establish dietary potassium control of insulin secretion. cross_nutrient: Carbohydrate metabolism regulates a potassium conductance rather than proving potassium supplementation benefit. [ashcroft-1984-glucose] Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells (1984). https://www.nature.com/articles/312446a0 DOI: 10.1038/312446a0

experimental_model

Primed mouse macrophages, extracellular-K titration.

exposure

Artificial extracellular potassium elevation; not dietary excess.

limitations

Stimulus-specific; does not justify elevating blood potassium.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mouse

plain_language

Reducing the outward potassium gradient blocked these activation routes.

primary_references

[munoz-2013-nlrp3] K+ efflux is the Common Trigger of NLRP3 inflammasome Activation by Bacterial Toxins and Particulate Matter (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3730833/ DOI: 10.1016/j.immuni.2013.05.016

tissue_or_cell_type

Bone-marrow macrophages

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 868–878

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primed mouse macrophages, extracellular-K titration. · source_derived_draft · unverified_draft

### k-high-medium-nlrp3-block Raising extracellular K to 45 mM maximally inhibited NLRP3 responses to the tested toxins and particles. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing the outward potassium gradient blocked these activation routes. organism: Mouse tissue_or_cell_type: Bone-marrow macrophages experimental_model: Primed mouse macrophages, extracellular-K titration. limitations: Stimulus-specific; does not justify elevating blood potassium. exposure: Artificial extracellular potassium elevation; not dietary excess. [munoz-2013-nlrp3] K+ efflux is the Common Trigger of NLRP3 inflammasome Activation by Bacterial Toxins and Particulate Matter (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3730833/ DOI: 10.1016/j.immuni.2013.05.016

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Knock-in mouse fiber voltage clamp.

limitations

The leak is not equivalent to the normal calcium-conducting pore.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mouse

plain_language

An inherited calcium-channel variant added an abnormal leak.

primary_references

[wu-2012-hypopp] A calcium channel mutant mouse model of hypokalemic periodic paralysis (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3533564/ DOI: 10.1172/JCI66091

tissue_or_cell_type

Skeletal muscle

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 751–760

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Knock-in mouse fiber voltage clamp. · source_derived_draft · unverified_draft

### k-hypopp-gating-pore R528H mouse fibers displayed anomalous inward current at resting potentials, supporting a voltage-sensor leak mechanism. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inherited calcium-channel variant added an abnormal leak. organism: Mouse tissue_or_cell_type: Skeletal muscle experimental_model: Knock-in mouse fiber voltage clamp. limitations: The leak is not equivalent to the normal calcium-conducting pore. [wu-2012-hypopp] A calcium channel mutant mouse model of hypokalemic periodic paralysis (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3533564/ DOI: 10.1172/JCI66091

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

A calcium-channel genetic defect changes potassium sensitivity of sodium-dependent muscle excitability.

experimental_model

4.75 to 2 mM K challenge; mouse muscle recordings.

limitations

Sex/genotype influenced susceptibility; no general dietary-paralysis claim.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mouse

plain_language

The same low-potassium exposure acted differently with inherited channel impairment.

primary_references

[wu-2012-hypopp] A calcium channel mutant mouse model of hypokalemic periodic paralysis (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3533564/ DOI: 10.1172/JCI66091

tissue_or_cell_type

Skeletal muscle

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 762–772

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 4.75 to 2 mM K challenge; mouse muscle recordings. · source_derived_draft · unverified_draft

### k-hypopp-low-k-depolarization At 2 mM bath K, R528H muscle paradoxically depolarized and lost force while wild-type fibers hyperpolarized. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same low-potassium exposure acted differently with inherited channel impairment. organism: Mouse tissue_or_cell_type: Skeletal muscle experimental_model: 4.75 to 2 mM K challenge; mouse muscle recordings. limitations: Sex/genotype influenced susceptibility; no general dietary-paralysis claim. cross_nutrient: A calcium-channel genetic defect changes potassium sensitivity of sodium-dependent muscle excitability. [wu-2012-hypopp] A calcium channel mutant mouse model of hypokalemic periodic paralysis (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3533564/ DOI: 10.1172/JCI66091

experimental_model

Myeloid-cell inflammasome experiments using imiquimod and CL097, potassium-efflux tests and mitochondrial target analysis.

limitations

Stimulus-specific boundary, not opposing evidence for the toxin/particle experiments.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mouse experimental systems

plain_language

Some drug-triggered inflammasome routes bypass potassium loss.

primary_references

[gross-2016-independent] K+ Efflux-Independent NLRP3 Inflammasome Activation by Small Molecules Targeting Mitochondria (2016). https://pubmed.ncbi.nlm.nih.gov/27692612/ DOI: 10.1016/j.immuni.2016.08.010

tissue_or_cell_type

Myeloid cells

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 891–900

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Myeloid-cell inflammasome experiments using imiquimod and CL097, potassium-efflux tests and mitochondrial target analysis. · source_derived_draft · unverified_draft

### k-independent-drug-nlrp3 Imiquimod and CL097 activated NLRP3 without requiring potassium efflux in the studied myeloid-cell experiments. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some drug-triggered inflammasome routes bypass potassium loss. organism: Mouse experimental systems tissue_or_cell_type: Myeloid cells experimental_model: Myeloid-cell inflammasome experiments using imiquimod and CL097, potassium-efflux tests and mitochondrial target analysis. limitations: Stimulus-specific boundary, not opposing evidence for the toxin/particle experiments. [gross-2016-independent] K+ Efflux-Independent NLRP3 Inflammasome Activation by Small Molecules Targeting Mitochondria (2016). https://pubmed.ncbi.nlm.nih.gov/27692612/ DOI: 10.1016/j.immuni.2016.08.010

cross_nutrient

Hormonal stimulation coordinates sodium extrusion and potassium entry.

experimental_model

Rat soleus in 85 mM Na/9 mM K.

limitations

Ex vivo rescue is not a clinical intervention recommendation.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rat

plain_language

Stimulating the shared sodium-potassium pump improved muscle responses.

primary_references

[overgaard-1999-muscle] Relations between excitability and contractility in rat soleus muscle: role of the Na+-K+ pump and Na+/K+ gradients (1999). https://pubmed.ncbi.nlm.nih.gov/10373703/ DOI: 10.1111/j.1469-7793.1999.0215r.x

tissue_or_cell_type

Soleus muscle

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 727–737

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat soleus in 85 mM Na/9 mM K. · source_derived_draft · unverified_draft

### k-insulin-muscle-pump-rescue Insulin stimulation of active Na-K transport restored M-wave area and force in the reduced-gradient soleus preparation. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Stimulating the shared sodium-potassium pump improved muscle responses. organism: Rat tissue_or_cell_type: Soleus muscle experimental_model: Rat soleus in 85 mM Na/9 mM K. limitations: Ex vivo rescue is not a clinical intervention recommendation. cross_nutrient: Hormonal stimulation coordinates sodium extrusion and potassium entry. [overgaard-1999-muscle] Relations between excitability and contractility in rat soleus muscle: role of the Na+-K+ pump and Na+/K+ gradients (1999). https://pubmed.ncbi.nlm.nih.gov/10373703/ DOI: 10.1111/j.1469-7793.1999.0215r.x

experimental_model

Mouse endothelial knockout and cortical flow measurement.

limitations

Residual responses require other contributors; no cognitive or dietary outcome tested.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

This potassium-sensing pathway contributed to activity-linked blood supply but did not account for all of it.

primary_references

[k-longden2017] Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow (2017). https://pubmed.ncbi.nlm.nih.gov/28319610/ DOI: 10.1038/nn.4533

tissue_or_cell_type

Cerebral microcirculation

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1616–1625

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse endothelial knockout and cortical flow measurement. · source_derived_draft · unverified_draft

### k-kir21-functional-hyperemia Endothelial Kir2.1 deletion reduced whisker-stimulation cerebral blood-flow responses by roughly half. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This potassium-sensing pathway contributed to activity-linked blood supply but did not account for all of it. organism: Mus musculus tissue_or_cell_type: Cerebral microcirculation experimental_model: Mouse endothelial knockout and cortical flow measurement. limitations: Residual responses require other contributors; no cognitive or dietary outcome tested. [k-longden2017] Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow (2017). https://pubmed.ncbi.nlm.nih.gov/28319610/ DOI: 10.1038/nn.4533

cross_nutrient

MgADP supplies a magnesium-dependent regulatory input to potassium conductance.

experimental_model

Xenopus oocyte cloned-channel patches.

limitations

Heterologous channel biochemistry, not nutritional magnesium depletion.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Xenopus expression system

plain_language

Magnesium-bound ADP helps keep this potassium channel active.

primary_references

[gribble-1997-sur1] The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC1169713/ DOI: 10.1093/emboj/16.6.1145

tissue_or_cell_type

Oocyte membrane

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 810–820

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Xenopus oocyte cloned-channel patches. · source_derived_draft · unverified_draft

### k-mgadp-sur1-activation MgADP potentiated cloned Kir6.2/SUR1 current through intact SUR1 nucleotide-binding machinery. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium-bound ADP helps keep this potassium channel active. organism: Xenopus expression system tissue_or_cell_type: Oocyte membrane experimental_model: Xenopus oocyte cloned-channel patches. limitations: Heterologous channel biochemistry, not nutritional magnesium depletion. cross_nutrient: MgADP supplies a magnesium-dependent regulatory input to potassium conductance. [gribble-1997-sur1] The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC1169713/ DOI: 10.1093/emboj/16.6.1145

experimental_model

Five-day feeding periods.

exposure

Added 20, 40 or 60 mEq/day; fries evaluated separately.

limitations

Specific foods and healthy participants; does not rank all foods or establish long-term outcomes.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

Potassium in the tested food and salt both reached the body.

primary_references

[k-macdonald2016] Bioavailability of potassium from potatoes and potassium gluconate: a randomized dose response trial (2016). https://pubmed.ncbi.nlm.nih.gov/27413123/ DOI: 10.3945/ajcn.115.127225

tissue_or_cell_type

Gastrointestinal tract; modeled balance

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1452–1462

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-day feeding periods. · source_derived_draft · unverified_draft

### k-potato-gluconate-absorption Modeled potassium absorption was high and not detectably different between potatoes and gluconate in the short feeding comparison. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium in the tested food and salt both reached the body. organism: Homo sapiens tissue_or_cell_type: Gastrointestinal tract; modeled balance experimental_model: Five-day feeding periods. limitations: Specific foods and healthy participants; does not rank all foods or establish long-term outcomes. exposure: Added 20, 40 or 60 mEq/day; fries evaluated separately. [k-macdonald2016] Bioavailability of potassium from potatoes and potassium gluconate: a randomized dose response trial (2016). https://pubmed.ncbi.nlm.nih.gov/27413123/ DOI: 10.3945/ajcn.115.127225

experimental_model

Same feeding study.

limitations

Urinary potassium alone is not an exact measure of food intake or intracellular stores.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

Urinary recovery and absorption are related but distinct measurements.

primary_references

[k-macdonald2016] Bioavailability of potassium from potatoes and potassium gluconate: a randomized dose response trial (2016). https://pubmed.ncbi.nlm.nih.gov/27413123/ DOI: 10.3945/ajcn.115.127225

tissue_or_cell_type

Urine and serum

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1464–1473

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same feeding study. · source_derived_draft · unverified_draft

### k-potato-urinary-recovery Urinary potassium recovery was greater after potato intake than after the supplement despite no detected source difference in serum exposure. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Urinary recovery and absorption are related but distinct measurements. organism: Homo sapiens tissue_or_cell_type: Urine and serum experimental_model: Same feeding study. limitations: Urinary potassium alone is not an exact measure of food intake or intracellular stores. [k-macdonald2016] Bioavailability of potassium from potatoes and potassium gluconate: a randomized dose response trial (2016). https://pubmed.ncbi.nlm.nih.gov/27413123/ DOI: 10.3945/ajcn.115.127225

cross_nutrient

Sodium export couples to potassium-supported pump cycling and magnesium-dependent energy use.

experimental_model

Radiotracer sodium and ATP-hydrolysis assay.

limitations

This measurement does not itself establish an exact two-potassium ratio.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Human

plain_language

ATP consumption pays for sodium extrusion while potassium is available externally.

primary_references

[garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

tissue_or_cell_type

Erythrocyte membrane

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 587–597

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiotracer sodium and ATP-hydrolysis assay. · source_derived_draft · unverified_draft

### k-pump-sodium-atp-coupling Ouabain-sensitive extrusion was approximately three sodium ions per ATP hydrolyzed in resealed erythrocyte ghosts. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP consumption pays for sodium extrusion while potassium is available externally. organism: Human tissue_or_cell_type: Erythrocyte membrane experimental_model: Radiotracer sodium and ATP-hydrolysis assay. limitations: This measurement does not itself establish an exact two-potassium ratio. cross_nutrient: Sodium export couples to potassium-supported pump cycling and magnesium-dependent energy use. [garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

experimental_model

Purified pig renal Na,K-ATPase; 3.5 angstrom crystallography with rubidium.

limitations

Rubidium is a congener; a static purified structure is not a dietary depletion test.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Pig

plain_language

The pump has two sites that can trap a potassium-like ion during transport.

primary_references

[morth-2007-pump] Crystal structure of the sodium-potassium pump (2007). https://pubmed.ncbi.nlm.nih.gov/18075585/ DOI: 10.1038/nature06419

tissue_or_cell_type

Renal membrane enzyme

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 599–608

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified pig renal Na,K-ATPase; 3.5 angstrom crystallography with rubidium. · source_derived_draft · unverified_draft

### k-pump-two-occluded-sites The pig pump structure resolved two occluded rubidium ions at potassium transport sites in its alpha subunit. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pump has two sites that can trap a potassium-like ion during transport. organism: Pig tissue_or_cell_type: Renal membrane enzyme experimental_model: Purified pig renal Na,K-ATPase; 3.5 angstrom crystallography with rubidium. limitations: Rubidium is a congener; a static purified structure is not a dietary depletion test. [morth-2007-pump] Crystal structure of the sodium-potassium pump (2007). https://pubmed.ncbi.nlm.nih.gov/18075585/ DOI: 10.1038/nature06419

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Single case; symptoms resolved after colectomy.

limitations

The proposed shock/ischemia-to-BK chain remains a hypothesis.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

Severe potassium loss can occur through the gut even in kidney failure.

primary_references

[k-van-dinter2008] Over-expression of colonic K+ channels associated with severe potassium secretory diarrhoea after haemorrhagic shock (2008). https://pubmed.ncbi.nlm.nih.gov/18653901/ DOI: 10.1093/ndt/gfn411

tissue_or_cell_type

Human colon

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1498–1507

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single case; symptoms resolved after colectomy. · source_derived_draft · unverified_draft

### k-secretory-diarrhea-bk-case Marked BK overexpression accompanied colonic potassium-secretory diarrhea and hypokalemia in the reported patient. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe potassium loss can occur through the gut even in kidney failure. organism: Homo sapiens tissue_or_cell_type: Human colon experimental_model: Single case; symptoms resolved after colectomy. limitations: The proposed shock/ischemia-to-BK chain remains a hypothesis. [k-van-dinter2008] Over-expression of colonic K+ channels associated with severe potassium secretory diarrhoea after haemorrhagic shock (2008). https://pubmed.ncbi.nlm.nih.gov/18653901/ DOI: 10.1093/ndt/gfn411

cross_nutrient

Combined sodium reduction/potassium increase; not potassium-alone molecular causation.

experimental_model

Cluster-randomized trial; mean 4.74-year follow-up.

limitations

Both sodium and potassium changed, so their effects cannot be separated. Serious kidney disease and potassium-sparing drugs/supplements were excluded; no serial serum-potassium surveillance.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

Replacing part of sodium chloride with potassium chloride improved a clinical outcome in the studied population.

primary_references

[k-neal2021] Effect of Salt Substitution on Cardiovascular Events and Death (2021). https://pubmed.ncbi.nlm.nih.gov/34459569/ DOI: 10.1056/nejmoa2105675

tissue_or_cell_type

Clinical cerebrovascular outcome

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1697–1707

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cluster-randomized trial; mean 4.74-year follow-up. · source_derived_draft · unverified_draft

### k-sodium-potassium-salt-stroke-trial The 75% NaCl/25% KCl salt substitute reduced stroke incidence versus ordinary salt in SSaSS (rate ratio 0.86). Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing part of sodium chloride with potassium chloride improved a clinical outcome in the studied population. organism: Homo sapiens tissue_or_cell_type: Clinical cerebrovascular outcome experimental_model: Cluster-randomized trial; mean 4.74-year follow-up. limitations: Both sodium and potassium changed, so their effects cannot be separated. Serious kidney disease and potassium-sparing drugs/supplements were excluded; no serial serum-potassium surveillance. cross_nutrient: Combined sodium reduction/potassium increase; not potassium-alone molecular causation. [k-neal2021] Effect of Salt Substitution on Cardiovascular Events and Death (2021). https://pubmed.ncbi.nlm.nih.gov/34459569/ DOI: 10.1056/nejmoa2105675

experimental_model

Engineered T cells, culture and adoptive transfer.

limitations

Genetic cell intervention cannot be translated into a dietary potassium claim.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mouse with human-cell complementary assays

plain_language

Increasing potassium exit rescued cells in this tumor model.

primary_references

[eil-2016-tcells] Ionic immune suppression within the tumour microenvironment limits T cell effector function (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5204372/ DOI: 10.1038/nature19364

tissue_or_cell_type

Tumor-infiltrating T cells

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 913–922

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered T cells, culture and adoptive transfer. · source_derived_draft · unverified_draft

### k-tcell-kv13-efflux Kv1.3 overexpression lowered intracellular K and improved antitumor T-cell function; engineered cells improved melanoma control in mice. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Increasing potassium exit rescued cells in this tumor model. organism: Mouse with human-cell complementary assays tissue_or_cell_type: Tumor-infiltrating T cells experimental_model: Engineered T cells, culture and adoptive transfer. limitations: Genetic cell intervention cannot be translated into a dietary potassium claim. [eil-2016-tcells] Ionic immune suppression within the tumour microenvironment limits T cell effector function (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5204372/ DOI: 10.1038/nature19364

cross_nutrient

Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation.

endpoint

Potassium bicarbonate increased urine citrate excretion and clearance in the same comparison.

experimental-exposure

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

experimental_model

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

limitations

Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

An alkali salt without administered citrate reproduced the citraturic response.

primary_references

[sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

tissue_or_cell_type

kidney and urine

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1232–1244

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. · source_derived_draft · unverified_draft

### kbicarbonate-increases-urine-citrate Potassium bicarbonate increased urine citrate excretion and clearance in the same comparison. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An alkali salt without administered citrate reproduced the citraturic response. organism: Homo sapiens tissue_or_cell_type: kidney and urine experimental_model: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. limitations: Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone. cross_nutrient: Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation. experimental-exposure: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. endpoint: Potassium bicarbonate increased urine citrate excretion and clearance in the same comparison. [sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

cross_nutrient

Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation.

endpoint

Potassium chloride did not significantly raise urinary citrate in these participants without potassium deficiency.

experimental-exposure

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

experimental_model

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

limitations

Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

Additional potassium without alkali did not reproduce the citrate response in this group.

primary_references

[sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

tissue_or_cell_type

kidney and urine

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1246–1258

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. · source_derived_draft · unverified_draft

### kchloride-no-citraturia-nondepleted Potassium chloride did not significantly raise urinary citrate in these participants without potassium deficiency. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Additional potassium without alkali did not reproduce the citrate response in this group. organism: Homo sapiens tissue_or_cell_type: kidney and urine experimental_model: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. limitations: Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone. cross_nutrient: Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation. experimental-exposure: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. endpoint: Potassium chloride did not significantly raise urinary citrate in these participants without potassium deficiency. [sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

cross_nutrient

Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation.

endpoint

Potassium citrate increased urine citrate excretion and clearance in the small stone-patient comparison.

experimental-exposure

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

experimental_model

Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day.

limitations

Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

This salt raised citrate availability in urine, with accompanying alkali delivery.

primary_references

[sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

tissue_or_cell_type

kidney and urine

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1218–1230

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. · source_derived_draft · unverified_draft

### kcitrate-increases-urine-citrate Potassium citrate increased urine citrate excretion and clearance in the small stone-patient comparison. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This salt raised citrate availability in urine, with accompanying alkali delivery. organism: Homo sapiens tissue_or_cell_type: kidney and urine experimental_model: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. limitations: Eight patients, short intervention; absence of potassium deficiency limits extrapolation to depletion. Alkali and citrate coeffects cannot be assigned to potassium cation alone. cross_nutrient: Potassium-salt anion determines effects on urinary citrate, which participates in calcium complexation. experimental-exposure: Eight patients with stones, without potassium deficiency, compared after two weeks of potassium citrate, bicarbonate, or chloride at 80 mEq/day. endpoint: Potassium citrate increased urine citrate excretion and clearance in the small stone-patient comparison. [sakhaee-1991-salts] Contrasting effects of various potassium salts on renal citrate excretion (1991). https://pubmed.ncbi.nlm.nih.gov/1899422/ DOI: 10.1210/jcem-72-2-396

endpoint

Beta-hydroxybutyric acid infusion increased portal insulin in conscious dogs.

experimental-exposure

Twelve conscious dogs with portal/hepatic/systemic sampling; beta-hydroxybutyric acid 7 mEq/kg or HCl 3 mEq/kg infused over 30 minutes; additional anesthetized and obstructed-urinary-tract studies.

experimental_model

Twelve conscious dogs with portal/hepatic/systemic sampling; beta-hydroxybutyric acid 7 mEq/kg or HCl 3 mEq/kg infused over 30 minutes; additional anesthetized and obstructed-urinary-tract studies.

limitations

Racemic ketone-acid infusion into nondiabetic animals does not model insulin-deficient diabetic ketoacidosis.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Canis lupus familiaris

plain_language

The ketone-acid intervention changed the hormone environment that controls potassium distribution.

primary_references

[adrogue-1985-acid-infusion] Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs (1985). https://www.jci.org/articles/view/111775 DOI: 10.1172/JCI111775

tissue_or_cell_type

pancreatic-portal circulation

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1164–1175

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve conscious dogs with portal/hepatic/systemic sampling; beta-hydroxybutyric acid 7 mEq/kg or HCl 3 mEq/kg infused over 30 minutes; additional anesthetized and obstructed-urinary-tract studies. · source_derived_draft · unverified_draft

### ketoacid-infusion-raises-portal-insulin Beta-hydroxybutyric acid infusion increased portal insulin in conscious dogs. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The ketone-acid intervention changed the hormone environment that controls potassium distribution. organism: Canis lupus familiaris tissue_or_cell_type: pancreatic-portal circulation experimental_model: Twelve conscious dogs with portal/hepatic/systemic sampling; beta-hydroxybutyric acid 7 mEq/kg or HCl 3 mEq/kg infused over 30 minutes; additional anesthetized and obstructed-urinary-tract studies. limitations: Racemic ketone-acid infusion into nondiabetic animals does not model insulin-deficient diabetic ketoacidosis. experimental-exposure: Twelve conscious dogs with portal/hepatic/systemic sampling; beta-hydroxybutyric acid 7 mEq/kg or HCl 3 mEq/kg infused over 30 minutes; additional anesthetized and obstructed-urinary-tract studies. endpoint: Beta-hydroxybutyric acid infusion increased portal insulin in conscious dogs. [adrogue-1985-acid-infusion] Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs (1985). https://www.jci.org/articles/view/111775 DOI: 10.1172/JCI111775

cross_nutrient

Citrate/alkali coadministration with potassium modifies calcium-stone formation in hypocitraturic stone formers.

endpoint

Potassium citrate reduced new stone formation relative to placebo among participants followed for three years in the hypocitraturic calcium-stone trial.

experimental-exposure

Fifty-seven people with recurrent calcium stones and hypocitraturia randomized to potassium citrate 30-60 mEq/day or placebo; three-year outcomes in 18 and 20 respectively.

experimental_model

Fifty-seven people with recurrent calcium stones and hypocitraturia randomized to potassium citrate 30-60 mEq/day or placebo; three-year outcomes in 18 and 20 respectively.

limitations

57 randomized but 38 contributed the cited three-year comparison; potassium, citrate and alkalinization were cointerventions. Not a potassium-cation-only effect or treatment recommendation.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

The combined salt changed a stone outcome in a selected clinical group.

primary_references

[barcelo-1993-stones] Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis (1993). https://www.sciencedirect.com/science/article/pii/S0022534717358883 DOI: 10.1016/S0022-5347(17)35888-3

tissue_or_cell_type

urinary tract

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1438–1450

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fifty-seven people with recurrent calcium stones and hypocitraturia randomized to potassium citrate 30-60 mEq/day or placebo; three-year outcomes in 18 and 20 respectively. · source_derived_draft · unverified_draft

### potassium-citrate-reduces-calcium-stone-formation Potassium citrate reduced new stone formation relative to placebo among participants followed for three years in the hypocitraturic calcium-stone trial. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combined salt changed a stone outcome in a selected clinical group. organism: Homo sapiens tissue_or_cell_type: urinary tract experimental_model: Fifty-seven people with recurrent calcium stones and hypocitraturia randomized to potassium citrate 30-60 mEq/day or placebo; three-year outcomes in 18 and 20 respectively. limitations: 57 randomized but 38 contributed the cited three-year comparison; potassium, citrate and alkalinization were cointerventions. Not a potassium-cation-only effect or treatment recommendation. cross_nutrient: Citrate/alkali coadministration with potassium modifies calcium-stone formation in hypocitraturic stone formers. experimental-exposure: Fifty-seven people with recurrent calcium stones and hypocitraturia randomized to potassium citrate 30-60 mEq/day or placebo; three-year outcomes in 18 and 20 respectively. endpoint: Potassium citrate reduced new stone formation relative to placebo among participants followed for three years in the hypocitraturic calcium-stone trial. [barcelo-1993-stones] Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis (1993). https://www.sciencedirect.com/science/article/pii/S0022534717358883 DOI: 10.1016/S0022-5347(17)35888-3

cross_nutrient

Local calcium availability permits flow-stimulated potassium secretion.

evidence_location

Results; luminal Ca and intracellular buffering experiments.

experimental_model

Luminal Ca removal/BAPTA and flow challenge

limitations

Tests ion availability in vitro, not dietary calcium deficiency; the entry-channel identity was unresolved.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Oryctolagus cuniculus

plain_language

Calcium entry and signaling are required for this flow-driven potassium output.

primary_references

[liu-2007-calcium-flow] Ca2+ dependence of flow-stimulated K secretion in the mammalian cortical collecting duct (2007). https://journals.physiology.org/doi/10.1152/ajprenal.00057.2007 DOI: 10.1152/ajprenal.00057.2007

tissue_or_cell_type

Cortical collecting duct

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 369–380

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Luminal Ca removal/BAPTA and flow challenge · source_derived_draft · unverified_draft

### renal-calcium-entry-supports-flow-k-secretion Removing luminal Ca2+ or buffering intracellular Ca2+ suppressed flow-stimulated K secretion in microperfused rabbit CCDs. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium entry and signaling are required for this flow-driven potassium output. organism: Oryctolagus cuniculus tissue_or_cell_type: Cortical collecting duct experimental_model: Luminal Ca removal/BAPTA and flow challenge limitations: Tests ion availability in vitro, not dietary calcium deficiency; the entry-channel identity was unresolved. cross_nutrient: Local calcium availability permits flow-stimulated potassium secretion. evidence_location: Results; luminal Ca and intracellular buffering experiments. [liu-2007-calcium-flow] Ca2+ dependence of flow-stimulated K secretion in the mammalian cortical collecting duct (2007). https://journals.physiology.org/doi/10.1152/ajprenal.00057.2007 DOI: 10.1152/ajprenal.00057.2007

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Cellular K depletion decreases magnesium entry in this DCT model.

evidence_location

Primary abstract; potassium-depleted-cell Mg uptake comparison.

experimental_model

Cultured MDCT potassium depletion; fluorescence Mg-recovery assay

limitations

Intracellular depletion is distinct from low extracellular K alone; TRPM6 was not identified.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus cell line

plain_language

Depleting cellular potassium made it harder for these kidney cells to take up magnesium.

primary_references

[dai-1997-k-mg] Cellular mechanisms of chlorothiazide and cellular potassium depletion on Mg2+ uptake in mouse distal convoluted tubule cells (1997). https://pubmed.ncbi.nlm.nih.gov/9083264/ DOI: 10.1038/ki.1997.141

tissue_or_cell_type

Distal convoluted tubule cell model

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 484–495

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured MDCT potassium depletion; fluorescence Mg-recovery assay · source_derived_draft · unverified_draft

### renal-cellular-k-depletion-lowers-mg-influx Potassium-depleted MDCT cells showed reduced Mg2+ uptake in a magnesium-recovery assay. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Depleting cellular potassium made it harder for these kidney cells to take up magnesium. organism: Mus musculus cell line tissue_or_cell_type: Distal convoluted tubule cell model experimental_model: Cultured MDCT potassium depletion; fluorescence Mg-recovery assay limitations: Intracellular depletion is distinct from low extracellular K alone; TRPM6 was not identified. cross_nutrient: Cellular K depletion decreases magnesium entry in this DCT model. evidence_location: Primary abstract; potassium-depleted-cell Mg uptake comparison. [dai-1997-k-mg] Cellular mechanisms of chlorothiazide and cellular potassium depletion on Mg2+ uptake in mouse distal convoluted tubule cells (1997). https://pubmed.ncbi.nlm.nih.gov/9083264/ DOI: 10.1038/ki.1997.141

cross_nutrient

Sodium transport through ENaC supports potassium secretion.

evidence_location

Figure 7 and associated Results.

experimental_model

Benzamil pretreatment and flow increase

limitations

Other species/segments can show ENaC-independent components; no universal requirement claimed.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Oryctolagus cuniculus

plain_language

Sodium entry through ENaC supports potassium secretion in this perfused segment.

primary_references

[liu-2007-calcium-flow] Ca2+ dependence of flow-stimulated K secretion in the mammalian cortical collecting duct (2007). https://journals.physiology.org/doi/10.1152/ajprenal.00057.2007 DOI: 10.1152/ajprenal.00057.2007

tissue_or_cell_type

Cortical collecting duct

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 382–393

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Benzamil pretreatment and flow increase · source_derived_draft · unverified_draft

### renal-enac-supports-rabbit-flow-k-secretion Benzamil inhibition of sodium absorption abolished the flow-stimulated increase in K secretion in rabbit CCDs. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium entry through ENaC supports potassium secretion in this perfused segment. organism: Oryctolagus cuniculus tissue_or_cell_type: Cortical collecting duct experimental_model: Benzamil pretreatment and flow increase limitations: Other species/segments can show ENaC-independent components; no universal requirement claimed. cross_nutrient: Sodium transport through ENaC supports potassium secretion. evidence_location: Figure 7 and associated Results. [liu-2007-calcium-flow] Ca2+ dependence of flow-stimulated K secretion in the mammalian cortical collecting duct (2007). https://journals.physiology.org/doi/10.1152/ajprenal.00057.2007 DOI: 10.1152/ajprenal.00057.2007

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

Human biomarker evidence links increased KCl intake to altered NaCl-transporter regulation.

evidence_location

Primary abstract; randomized crossover uEV immunoblots.

experimental_model

Five-day crossover phases; 18 analyzed healthy participants; controlled high-Na/low-K diet

limitations

Vesicle cargo is an indirect renal readout; no dietary recommendation or direct transport-flux inference.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

A human urine marker of the sodium-chloride transporter fell when potassium intake increased.

primary_references

[wu-2023-human-ncc] Randomized Trial on the Effect of Oral Potassium Chloride Supplementation on the Thiazide-Sensitive Sodium Chloride Cotransporter in Healthy Adults (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10239795/ DOI: 10.1016/j.ekir.2023.03.011

tissue_or_cell_type

Urinary extracellular vesicles

trigger_kind

biomarker_context Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 535–546

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five-day crossover phases; 18 analyzed healthy participants; controlled high-Na/low-K diet · source_derived_draft · unverified_draft

### renal-human-kcl-lowers-uev-ncc Supplementary KCl lowered total and phosphorylated NCC in urinary extracellular vesicles versus placebo in a randomized crossover study. Condition category: biomarker_context nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A human urine marker of the sodium-chloride transporter fell when potassium intake increased. organism: Homo sapiens tissue_or_cell_type: Urinary extracellular vesicles experimental_model: Five-day crossover phases; 18 analyzed healthy participants; controlled high-Na/low-K diet limitations: Vesicle cargo is an indirect renal readout; no dietary recommendation or direct transport-flux inference. cross_nutrient: Human biomarker evidence links increased KCl intake to altered NaCl-transporter regulation. evidence_location: Primary abstract; randomized crossover uEV immunoblots. [wu-2023-human-ncc] Randomized Trial on the Effect of Oral Potassium Chloride Supplementation on the Thiazide-Sensitive Sodium Chloride Cotransporter in Healthy Adults (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10239795/ DOI: 10.1016/j.ekir.2023.03.011

evidence_location

Primary abstract; meal-plus-K and eplerenone comparisons.

experimental_model

Controlled meal challenges and MR-blockade comparison; 32 participants

limitations

Low-sodium controlled background; no gut receptor identified and complete aldosterone independence is an inference.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

People can increase potassium excretion after a meal before a measurable blood rise.

primary_references

[preston-2015-gut-human] Evidence for a gastrointestinal-renal kaliuretic signaling axis in humans (2015). https://pubmed.ncbi.nlm.nih.gov/26308672/ DOI: 10.1038/ki.2015.243

tissue_or_cell_type

Gastrointestinal-renal axis

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 472–482

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled meal challenges and MR-blockade comparison; 32 participants · source_derived_draft · unverified_draft

### renal-human-meal-k-excretion-without-serum-rise A potassium-containing meal increased K excretion without a detected serum K rise in the human study; the response persisted with eplerenone. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: People can increase potassium excretion after a meal before a measurable blood rise. organism: Homo sapiens tissue_or_cell_type: Gastrointestinal-renal axis experimental_model: Controlled meal challenges and MR-blockade comparison; 32 participants limitations: Low-sodium controlled background; no gut receptor identified and complete aldosterone independence is an inference. evidence_location: Primary abstract; meal-plus-K and eplerenone comparisons. [preston-2015-gut-human] Evidence for a gastrointestinal-renal kaliuretic signaling axis in humans (2015). https://pubmed.ncbi.nlm.nih.gov/26308672/ DOI: 10.1038/ki.2015.243

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

The K-depletion effect on Mg entry is partly recoverable by membrane polarization.

evidence_location

Primary abstract; SCN- rescue experiment.

experimental_model

SCN- voltage manipulation after cell K depletion

limitations

Supports partial voltage mediation; does not establish an in vivo repletion strategy.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus cell line

plain_language

Restoring the electrical driving force helped magnesium enter despite prior potassium depletion.

primary_references

[dai-1997-k-mg] Cellular mechanisms of chlorothiazide and cellular potassium depletion on Mg2+ uptake in mouse distal convoluted tubule cells (1997). https://pubmed.ncbi.nlm.nih.gov/9083264/ DOI: 10.1038/ki.1997.141

tissue_or_cell_type

Distal convoluted tubule cell model

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 497–508

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SCN- voltage manipulation after cell K depletion · source_derived_draft · unverified_draft

### renal-hyperpolarization-rescues-mg-after-k-depletion Thiocyanate-induced hyperpolarization restored Mg2+ uptake in potassium-depleted MDCT cells. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring the electrical driving force helped magnesium enter despite prior potassium depletion. organism: Mus musculus cell line tissue_or_cell_type: Distal convoluted tubule cell model experimental_model: SCN- voltage manipulation after cell K depletion limitations: Supports partial voltage mediation; does not establish an in vivo repletion strategy. cross_nutrient: The K-depletion effect on Mg entry is partly recoverable by membrane polarization. evidence_location: Primary abstract; SCN- rescue experiment. [dai-1997-k-mg] Cellular mechanisms of chlorothiazide and cellular potassium depletion on Mg2+ uptake in mouse distal convoluted tubule cells (1997). https://pubmed.ncbi.nlm.nih.gov/9083264/ DOI: 10.1038/ki.1997.141

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

A calcium-activated K channel connects tubular flow to K elimination.

evidence_location

Figure 5; sex context Figure 8.

experimental_model

Cell-specific knockout; high-K adaptation; microperfusion

limitations

Chronic blood K elevation occurred only in males; whole-animal urinary outputs showed compensation.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

Flow-dependent potassium secretion needs BK channels in intercalated cells.

primary_references

[carrisoza-2020-intercalated-bk] Intercalated cell BKalpha subunit is required for flow-induced K+ secretion (2020). https://insight.jci.org/articles/view/130553 DOI: 10.1172/jci.insight.130553

tissue_or_cell_type

CCD intercalated cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 356–367

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-specific knockout; high-K adaptation; microperfusion · source_derived_draft · unverified_draft

### renal-intercalated-bk-flow-secretion Intercalated-cell BKalpha deletion abolished flow-stimulated K secretion in isolated mouse CCDs from both sexes. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Flow-dependent potassium secretion needs BK channels in intercalated cells. organism: Mus musculus tissue_or_cell_type: CCD intercalated cells experimental_model: Cell-specific knockout; high-K adaptation; microperfusion limitations: Chronic blood K elevation occurred only in males; whole-animal urinary outputs showed compensation. cross_nutrient: A calcium-activated K channel connects tubular flow to K elimination. evidence_location: Figure 5; sex context Figure 8. [carrisoza-2020-intercalated-bk] Intercalated cell BKalpha subunit is required for flow-induced K+ secretion (2020). https://insight.jci.org/articles/view/130553 DOI: 10.1172/jci.insight.130553

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Primary abstract; K/Rb comparisons with buffer and secretion manipulation.

experimental_model

Clearance studies with amiloride and buffer-delivery manipulation

limitations

Clearance evidence does not identify the H,K-ATPase isoform or directly localize all transport.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rattus norvegicus

plain_language

The depleted kidney can increase potassium recovery; rubidium does not track it perfectly.

primary_references

[1992-k-reabsorption] Effect of K depletion on renal K and Rb excretion: evidence for activation of K reabsorption (1992). https://pubmed.ncbi.nlm.nih.gov/1405312/ DOI: 10.1038/ki.1992.286

tissue_or_cell_type

Kidney; distal absorptive pathway inferred

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 523–533

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clearance studies with amiloride and buffer-delivery manipulation · source_derived_draft · unverified_draft

### renal-k-depletion-activates-reabsorption K-depleted rats preferentially retained K over Rb, especially when distal buffer delivery increased and residual secretion was inhibited. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The depleted kidney can increase potassium recovery; rubidium does not track it perfectly. organism: Rattus norvegicus tissue_or_cell_type: Kidney; distal absorptive pathway inferred experimental_model: Clearance studies with amiloride and buffer-delivery manipulation limitations: Clearance evidence does not identify the H,K-ATPase isoform or directly localize all transport. evidence_location: Primary abstract; K/Rb comparisons with buffer and secretion manipulation. [1992-k-reabsorption] Effect of K depletion on renal K and Rb excretion: evidence for activation of K reabsorption (1992). https://pubmed.ncbi.nlm.nih.gov/1405312/ DOI: 10.1038/ki.1992.286

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Potassium conductance is needed to regulate apical sodium/chloride transport.

evidence_location

Abstract and Discussion; DCT patch-clamp experiments.

experimental_model

Inducible adult kidney-specific Kcnj10 deletion

limitations

Genetic loss is not dietary deficiency; Kir5.1 participation was not directly deleted in this study.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

Without Kir4.1, DCT cells lose the electrical response used to sense potassium.

primary_references

[cuevas-2017-kir4-sensing] Potassium Sensing by Renal Distal Tubules Requires Kir4.1 (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5461801/ DOI: 10.1681/ASN.2016090935

tissue_or_cell_type

DCT basolateral membrane

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 190–201

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible adult kidney-specific Kcnj10 deletion · source_derived_draft · unverified_draft

### renal-kir4-loss-disables-sensing Adult renal Kir4.1 deletion depolarized DCT cells and abolished their voltage response to plasma potassium. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Without Kir4.1, DCT cells lose the electrical response used to sense potassium. organism: Mus musculus tissue_or_cell_type: DCT basolateral membrane experimental_model: Inducible adult kidney-specific Kcnj10 deletion limitations: Genetic loss is not dietary deficiency; Kir5.1 participation was not directly deleted in this study. cross_nutrient: Potassium conductance is needed to regulate apical sodium/chloride transport. evidence_location: Abstract and Discussion; DCT patch-clamp experiments. [cuevas-2017-kir4-sensing] Potassium Sensing by Renal Distal Tubules Requires Kir4.1 (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5461801/ DOI: 10.1681/ASN.2016090935

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Defective sodium-channel regulation compromises K balance.

evidence_location

Abstract; Results Figures 1 and 5.

experimental_model

Inducible renal MR deletion

limitations

NCC remained activatable by K restriction; receptor effects on NCC are not assumed to be direct.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

The mineralocorticoid receptor helps maintain the sodium-channel machinery needed for normal potassium balance.

primary_references

[terker-2016-mineralocorticoid] Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4978056/ DOI: 10.1681/ASN.2015070815

tissue_or_cell_type

Aldosterone-sensitive distal nephron

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 395–406

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible renal MR deletion · source_derived_draft · unverified_draft

### renal-mr-supports-enac-processing Nephron-wide MR deletion impaired apical ENaC orientation/cleavage and produced hyperkalemia with salt wasting in adult mice. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mineralocorticoid receptor helps maintain the sodium-channel machinery needed for normal potassium balance. organism: Mus musculus tissue_or_cell_type: Aldosterone-sensitive distal nephron experimental_model: Inducible renal MR deletion limitations: NCC remained activatable by K restriction; receptor effects on NCC are not assumed to be direct. cross_nutrient: Defective sodium-channel regulation compromises K balance. evidence_location: Abstract; Results Figures 1 and 5. [terker-2016-mineralocorticoid] Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4978056/ DOI: 10.1681/ASN.2015070815

cross_nutrient

Potassium is a transported participant in this sodium/chloride entry mechanism.

evidence_location

Primary abstract; functional oocyte characterization.

experimental_model

Cloned renal cotransporter expression

limitations

Transport identity, not a dietary deficiency threshold; individual splice variants are not generalized.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mammalian proteins in Xenopus laevis oocytes

plain_language

NKCC2 moves potassium together with sodium and chloride; the related NCC transporter does not require potassium as cargo.

primary_references

[gamba-1994-nkcc2] Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney (1994). https://www.sciencedirect.com/science/article/pii/S0021925817324997 DOI: 10.1016/S0021-9258(17)32499-7

tissue_or_cell_type

Heterologous cell membrane

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 548–559

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloned renal cotransporter expression · source_derived_draft · unverified_draft

### renal-nkcc2-couples-potassium-to-salt-influx Cloned renal NKCC2 supported bumetanide-sensitive sodium-potassium-chloride cotransport in oocytes, distinct from NCC potassium-independent NaCl transport. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: NKCC2 moves potassium together with sodium and chloride; the related NCC transporter does not require potassium as cargo. organism: Mammalian proteins in Xenopus laevis oocytes tissue_or_cell_type: Heterologous cell membrane experimental_model: Cloned renal cotransporter expression limitations: Transport identity, not a dietary deficiency threshold; individual splice variants are not generalized. cross_nutrient: Potassium is a transported participant in this sodium/chloride entry mechanism. evidence_location: Primary abstract; functional oocyte characterization. [gamba-1994-nkcc2] Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney (1994). https://www.sciencedirect.com/science/article/pii/S0021925817324997 DOI: 10.1016/S0021-9258(17)32499-7

cross_nutrient

K loading suppresses a Na/Cl transporter before some hormonal adaptations.

evidence_location

Primary abstract; early NCC time course and aldosterone-deficient mice.

experimental_model

Gastric K load; aldosterone-deficient comparison

limitations

Early response differs from later ENaC activation; acute gavage is not a chronic diet.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

The earliest NCC response to potassium does not require a new aldosterone signal in this model.

primary_references

[sorensen-2013-oral-k-ncc] Rapid dephosphorylation of the renal sodium chloride cotransporter in response to oral potassium intake in mice (2013). https://pubmed.ncbi.nlm.nih.gov/23447069/ DOI: 10.1038/ki.2013.14

tissue_or_cell_type

Kidney DCT

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 294–305

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gastric K load; aldosterone-deficient comparison · source_derived_draft · unverified_draft

### renal-oral-k-aldosterone-independent-ncc-off Oral K rapidly dephosphorylated NCC in mice, including aldosterone-deficient animals. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The earliest NCC response to potassium does not require a new aldosterone signal in this model. organism: Mus musculus tissue_or_cell_type: Kidney DCT experimental_model: Gastric K load; aldosterone-deficient comparison limitations: Early response differs from later ENaC activation; acute gavage is not a chronic diet. cross_nutrient: K loading suppresses a Na/Cl transporter before some hormonal adaptations. evidence_location: Primary abstract; early NCC time course and aldosterone-deficient mice. [sorensen-2013-oral-k-ncc] Rapid dephosphorylation of the renal sodium chloride cotransporter in response to oral potassium intake in mice (2013). https://pubmed.ncbi.nlm.nih.gov/23447069/ DOI: 10.1038/ki.2013.14

cross_nutrient

K-dependent phosphatase engagement reduces the activation signal of the Na/Cl transporter.

evidence_location

Figure 6A-C.

experimental_model

Purified binding/phosphatase assays and MDCKI-hNCC cells

limitations

Binding/activity assays do not by themselves quantify sodium transport in humans.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Recombinant proteins; Canis lupus familiaris cell line expressing human NCC

plain_language

Potassium can increase contact between NCC and an enzyme that removes its phosphate signal.

primary_references

[grimm-2023-pp1a-ncc] Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure (2023). https://www.jci.org/articles/view/158498 DOI: 10.1172/JCI158498

tissue_or_cell_type

Cell-free and kidney-derived cells

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 268–279

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified binding/phosphatase assays and MDCKI-hNCC cells · source_derived_draft · unverified_draft

### renal-pp1a-dephosphorylates-ncc PP1A directly bound the NCC regulatory terminus and dephosphorylated NCC; high extracellular K enhanced their association in MDCKI-hNCC cells. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium can increase contact between NCC and an enzyme that removes its phosphate signal. organism: Recombinant proteins; Canis lupus familiaris cell line expressing human NCC tissue_or_cell_type: Cell-free and kidney-derived cells experimental_model: Purified binding/phosphatase assays and MDCKI-hNCC cells limitations: Binding/activity assays do not by themselves quantify sodium transport in humans. cross_nutrient: K-dependent phosphatase engagement reduces the activation signal of the Na/Cl transporter. evidence_location: Figure 6A-C. [grimm-2023-pp1a-ncc] Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure (2023). https://www.jci.org/articles/view/158498 DOI: 10.1172/JCI158498

evidence_location

Study 1 and primary abstract.

experimental_model

Meal comparison with plasma-profile-matched KCl infusion

limitations

The responsible sensor/factor was unidentified; matching sampled plasma does not exclude every local signal.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rattus norvegicus

plain_language

The meal-associated signal adds to the effect of potassium measured in blood.

primary_references

[oh-2011-gut-k] Gut sensing of dietary K+ intake increases renal K+ excretion (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3154709/ DOI: 10.1152/ajpregu.00095.2011

tissue_or_cell_type

Gastrointestinal-renal axis

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 460–470

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Meal comparison with plasma-profile-matched KCl infusion · source_derived_draft · unverified_draft

### renal-rat-meal-k-excretion-beyond-plasma Potassium-containing meals produced more renal K excretion than K-free meals plus intravenous KCl despite matched plasma K profiles in rats. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The meal-associated signal adds to the effect of potassium measured in blood. organism: Rattus norvegicus tissue_or_cell_type: Gastrointestinal-renal axis experimental_model: Meal comparison with plasma-profile-matched KCl infusion limitations: The responsible sensor/factor was unidentified; matching sampled plasma does not exclude every local signal. evidence_location: Study 1 and primary abstract. [oh-2011-gut-k] Gut sensing of dietary K+ intake increases renal K+ excretion (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3154709/ DOI: 10.1152/ajpregu.00095.2011

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Loss of potassium-channel machinery impairs sodium/chloride recovery.

evidence_location

Lorenz primary abstract: micropuncture; Lu Results: TAL patch-clamp.

experimental_model

Pan-Romk deletion; micropuncture and companion patch-clamp studies

limitations

Hydronephrosis, developmental disease and compensatory transport complicate whole-kidney endpoints.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

ROMK-mediated potassium recycling supports loop salt recovery, while residual salt transport survives its deletion.

primary_references

[lorenz-2002-romk-tal] Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome (2002). https://pubmed.ncbi.nlm.nih.gov/12122007/ DOI: 10.1074/jbc.M205627200 [lu-2002-romk-null] Absence of small conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter's) knockout mice (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC4426997/ DOI: 10.1074/jbc.M206644200

tissue_or_cell_type

Thick ascending limb

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 561–573

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pan-Romk deletion; micropuncture and companion patch-clamp studies · source_derived_draft · unverified_draft

### renal-romk-supports-tal-salt-reabsorption Romk-null mice had reduced, but persisting, TAL NaCl absorption by micropuncture; the companion study demonstrated loss of native apical small-conductance K channels. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ROMK-mediated potassium recycling supports loop salt recovery, while residual salt transport survives its deletion. organism: Mus musculus tissue_or_cell_type: Thick ascending limb experimental_model: Pan-Romk deletion; micropuncture and companion patch-clamp studies limitations: Hydronephrosis, developmental disease and compensatory transport complicate whole-kidney endpoints. cross_nutrient: Loss of potassium-channel machinery impairs sodium/chloride recovery. evidence_location: Lorenz primary abstract: micropuncture; Lu Results: TAL patch-clamp. [lorenz-2002-romk-tal] Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome (2002). https://pubmed.ncbi.nlm.nih.gov/12122007/ DOI: 10.1074/jbc.M205627200 [lu-2002-romk-null] Absence of small conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter's) knockout mice (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC4426997/ DOI: 10.1074/jbc.M206644200

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

A chloride-sensing defect disrupts K control of sodium transport.

evidence_location

Primary abstract; acute gavage NCC comparison.

experimental_model

Wnk4 LLFF knockin; oral K gavage

limitations

Constitutive kinase activation and longer-term K responses must be distinguished.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

Making WNK4 insensitive to chloride blocks the rapid potassium response in this mouse model.

primary_references

[chen-2019-wnk4-sensor] WNK4 kinase is a physiological intracellular chloride sensor (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6410802/ DOI: 10.1073/pnas.1817220116

tissue_or_cell_type

Kidney DCT

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 242–253

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wnk4 LLFF knockin; oral K gavage · source_derived_draft · unverified_draft

### renal-wnk4-chloride-mutant-blocks-acute-k-off Acute oral potassium failed to suppress NCC in mice carrying chloride-insensitive WNK4, unlike wild-type controls. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Making WNK4 insensitive to chloride blocks the rapid potassium response in this mouse model. organism: Mus musculus tissue_or_cell_type: Kidney DCT experimental_model: Wnk4 LLFF knockin; oral K gavage limitations: Constitutive kinase activation and longer-term K responses must be distinguished. cross_nutrient: A chloride-sensing defect disrupts K control of sodium transport. evidence_location: Primary abstract; acute gavage NCC comparison. [chen-2019-wnk4-sensor] WNK4 kinase is a physiological intracellular chloride sensor (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6410802/ DOI: 10.1073/pnas.1817220116

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Balance of kinase and phosphatase signaling controls Na/Cl transport responses to K.

evidence_location

Discussion; WNK4-LLFF HEK experiment and acute-versus-prolonged restriction comparison.

experimental_model

HEK mutant expression with complementary mouse/kidney-slice experiments

limitations

Inference about obligatory kinase shutdown is disputed; model and adaptation time matter.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens cell line; Mus musculus

plain_language

A strongly active kinase relay can keep NCC phosphorylated during an acute potassium challenge.

primary_references

[yang-2021-ncc-off-switch] Roles of WNK4 and SPAK in K+-mediated dephosphorylation of the NaCl cotransporter (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8174808/ DOI: 10.1152/ajprenal.00459.2020

tissue_or_cell_type

HEK cells and renal DCT

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 255–266

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK mutant expression with complementary mouse/kidney-slice experiments · source_derived_draft · unverified_draft

### renal-wnk4-spak-activation-opposes-acute-off Chloride-insensitive WNK4 blocked high-K NCC dephosphorylation in HEK cells; the authors inferred that WNK4-SPAK inhibition is required for the rapid response. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A strongly active kinase relay can keep NCC phosphorylated during an acute potassium challenge. organism: Homo sapiens cell line; Mus musculus tissue_or_cell_type: HEK cells and renal DCT experimental_model: HEK mutant expression with complementary mouse/kidney-slice experiments limitations: Inference about obligatory kinase shutdown is disputed; model and adaptation time matter. cross_nutrient: Balance of kinase and phosphatase signaling controls Na/Cl transport responses to K. evidence_location: Discussion; WNK4-LLFF HEK experiment and acute-versus-prolonged restriction comparison. [yang-2021-ncc-off-switch] Roles of WNK4 and SPAK in K+-mediated dephosphorylation of the NaCl cotransporter (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8174808/ DOI: 10.1152/ajprenal.00459.2020

evidence_access

Primary abstract

experimental_model

Hamster enzyme and membrane-vesicle controls.

limitations

Negative controls narrow the interpretation; they do not rule out every ion-transport effect.

nutrient_topic

Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia

plain_language

Reduced whole-tissue absorption did not identify a direct sodium-pump or brush-border transport block.

primary_references

Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7482583/ · DOI 10.1016/0378-4274(95)03391-w

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 354–360

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Hamster enzyme and membrane-vesicle controls. · source_derived_draft · unverified_draft

## stevia-hamster-pump-control Reduced whole-tissue absorption did not identify a direct sodium-pump or brush-border transport block. Steviol did not inhibit intestinal sodium-potassium ATPase activity or brush-border-vesicle glucose uptake in the hamster experiment. Model: Hamster enzyme and membrane-vesicle controls. Limitations: Negative controls narrow the interpretation; they do not rule out every ion-transport effect. Evidence access: Primary abstract Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7482583/ · DOI 10.1016/0378-4274(95)03391-w

evidence_access

Primary abstract

experimental_model

Mouse islets and rat INS-1 beta-cell experiments; channel findings summarized in the primary abstract.

limitations

The accessed abstract includes mouse islets and rat INS-1 cells but does not unambiguously assign the channel recording to one preparation; full protocol-level reconciliation with the later positive report is incomplete.

nutrient_topic

Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia

plain_language

One experiment found insulin stimulation without a detected potassium-channel effect.

primary_references

Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10690946/ · DOI 10.1016/s0026-0495(00)91325-8

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse islets and rat INS-1 beta-cell experiments; channel findings summarized in the primary abstract. · source_derived_draft · unverified_draft

## stevia-katp-null One experiment found insulin stimulation without a detected potassium-channel effect. Stevioside at 1–100 micromolar did not alter ATP-sensitive potassium-channel activity in the reported beta-cell experiments. Model: Mouse islets and rat INS-1 beta-cell experiments; channel findings summarized in the primary abstract. Limitations: The accessed abstract includes mouse islets and rat INS-1 cells but does not unambiguously assign the channel recording to one preparation; full protocol-level reconciliation with the later positive report is incomplete. Evidence access: Primary abstract Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10690946/ · DOI 10.1016/s0026-0495(00)91325-8

evidence_access

Primary abstract

experimental_model

Conventional and permeabilized whole-cell patch clamp of mouse islet beta cells.

limitations

This does not by itself establish direct pore binding; glucose dependence and recording conditions may explain the discrepancy.

nutrient_topic

Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia

plain_language

Another experiment detected a potassium-channel change at a concentration within the earlier tested range.

primary_references

Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18435771/ · DOI 10.1111/j.1463-1326.2008.00864.x

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 234–240

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Conventional and permeabilized whole-cell patch clamp of mouse islet beta cells. · source_derived_draft · unverified_draft

## stevia-katp-positive Another experiment detected a potassium-channel change at a concentration within the earlier tested range. Stevioside at 1 micromolar reduced ATP-sensitive potassium conductance in a glucose-dependent manner in dispersed mouse beta cells. Model: Conventional and permeabilized whole-cell patch clamp of mouse islet beta cells. Limitations: This does not by itself establish direct pore binding; glucose dependence and recording conditions may explain the discrepancy. Evidence access: Primary abstract Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18435771/ · DOI 10.1111/j.1463-1326.2008.00864.x

evidence_access

Primary full text; Figure 1 and patch-clamp methods

experimental_model

Whole-cell patch clamp with 1 micromolar free intracellular calcium.

limitations

Human host-cell origin does not establish construct species; that uncertainty is explicit in the channel node.

nutrient_topic

Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia

plain_language

It strengthens an existing ion-channel response rather than supplying the calcium signal.

primary_references

Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28361903/ · DOI 10.1038/ncomms14733

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 170–176

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Whole-cell patch clamp with 1 micromolar free intracellular calcium. · source_derived_draft · unverified_draft

## stevia-trpm5-stev It strengthens an existing ion-channel response rather than supplying the calcium signal. Stevioside increased calcium-activated TRPM5 currents in transfected HEK293T cells; the effect reversed with washout. Model: Whole-cell patch clamp with 1 micromolar free intracellular calcium. Limitations: Human host-cell origin does not establish construct species; that uncertainty is explicit in the channel node. Evidence access: Primary full text; Figure 1 and patch-clamp methods Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28361903/ · DOI 10.1038/ncomms14733

evidence_span

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experimental_model

Patch clamp and site-directed mutagenesis

exposure

Berberine concentration-response; hERG mutations

limitations

Different expression systems had markedly different IC50 values. Channel inhibition is a hazard mechanism, not an incidence estimate for arrhythmia in supplement users.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human hERG expressed in HEK293 cells and Xenopus oocytes

plain_language

A potassium channel needed for cardiac repolarization is a separate safety-related target.

primary_references

[berberine-p16424781] Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. (2006). https://pubmed.ncbi.nlm.nih.gov/16424781/ DOI: 10.1097/01.fjc.0000191564.52242.00

tissue_or_cell_type

Cardiac potassium-channel model

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 610–621

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patch clamp and site-directed mutagenesis · source_derived_draft · unverified_draft

### berberine-herg-block Berberine blocked hERG current, with IC50 about 3.1 micromolar in HEK293 cells and 80 micromolar in oocytes. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A potassium channel needed for cardiac repolarization is a separate safety-related target. organism: Human hERG expressed in HEK293 cells and Xenopus oocytes tissue_or_cell_type: Cardiac potassium-channel model experimental_model: Patch clamp and site-directed mutagenesis limitations: Different expression systems had markedly different IC50 values. Channel inhibition is a hazard mechanism, not an incidence estimate for arrhythmia in supplement users. exposure: Berberine concentration-response; hERG mutations evidence_span: {"source_cache": "artifacts/berberine-research/16424781.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "45057bbc2da5981b23041d50a91a8e0adacfc150adf66d23daac0402f8ead682", "start_char": 0, "end_char": 1322, "text_sha256": "45057bbc2da5981b23041d50a91a8e0adacfc150adf66d23daac0402f8ead682"} [berberine-p16424781] Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. (2006). https://pubmed.ncbi.nlm.nih.gov/16424781/ DOI: 10.1097/01.fjc.0000191564.52242.00

evidence_span

{"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"}

experimental_model

Ussing-chamber short-circuit current, patch clamp and kinase perturbation

exposure

Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar

limitations

Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human T84 colonic cells

plain_language

Reducing potassium recycling can limit chloride secretion across intestinal cells.

primary_references

[berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033

tissue_or_cell_type

Basolateral potassium recycling and chloride secretion

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 558–569

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ussing-chamber short-circuit current, patch clamp and kinase perturbation · source_derived_draft · unverified_draft

### berberine-kcnq1-current Berberine inhibited a cAMP-dependent, chromanol-sensitive basolateral potassium current consistent with KCNQ1 by 88%. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing potassium recycling can limit chloride secretion across intestinal cells. organism: Human T84 colonic cells tissue_or_cell_type: Basolateral potassium recycling and chloride secretion experimental_model: Ussing-chamber short-circuit current, patch clamp and kinase perturbation limitations: Intestinal cell mechanism, not proof of systemic potassium depletion. The observed channel complex differs from cardiac KCNQ1/KCNE1. exposure: Forskolin-stimulated secretion and berberine; IC50 about 80 micromolar evidence_span: {"source_cache": "artifacts/berberine-research/21747769.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4", "start_char": 0, "end_char": 1734, "text_sha256": "b8864a2844ea828aeabcfc05219050ac1cb6efe7f24c663dc3302887f7f59ad4"} [berberine-p21747769] Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels. (2011). https://pubmed.ncbi.nlm.nih.gov/21747769/ DOI: 10.3389/fphys.2011.00033

experimental_model

2025 SSKI manufacturer label; 1 g KI/mL formulation.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Label warning, not a quantified primary interaction trial; applicability depends on exposure and patient context.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

The potassium component matters when potassium excretion is impaired.

primary_references

SSKI product label, July 2025 · manufacturer label; DailyMed lists UNAPPROVED DRUG OTHER; not a trial or FDA approval · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca1d3449-ea29-49a4-8863-365ec95f1553

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 448–454

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · 2025 SSKI manufacturer label; 1 g KI/mL formulation. · source_derived_draft · unverified_draft

## ki-hyperkalemia The potassium component matters when potassium excretion is impaired. The SSKI label warns of hyperkalemia with potassium-containing drugs, potassium-sparing diuretics or ACE inhibitors. Model: 2025 SSKI manufacturer label; 1 g KI/mL formulation. Limitations: Label warning, not a quantified primary interaction trial; applicability depends on exposure and patient context. Evidence location: Primary abstract SSKI product label, July 2025 · manufacturer label; DailyMed lists UNAPPROVED DRUG OTHER; not a trial or FDA approval · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca1d3449-ea29-49a4-8863-365ec95f1553

experimental_model

Chemical formula KI; molar mass 166.0028 g/mol.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Stoichiometric calculation using K 39.0983 and I 126.9045 g/mol; not a dose recommendation.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

Milligrams of KI are not milligrams of iodine.

primary_references

NIST Chemistry WebBook: potassium iodide · chemical reference · https://webbook.nist.gov/cgi/cbook.cgi?ID=7681110

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 48–54

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Chemical formula KI; molar mass 166.0028 g/mol. · source_derived_draft · unverified_draft

## ki-mass Milligrams of KI are not milligrams of iodine. Calculated from formula masses, KI is about 76.45% iodine and 23.55% potassium by mass; 130 mg KI contains about 99.4 mg iodine and 30.6 mg potassium. Model: Chemical formula KI; molar mass 166.0028 g/mol. Limitations: Stoichiometric calculation using K 39.0983 and I 126.9045 g/mol; not a dose recommendation. Evidence location: Primary abstract NIST Chemistry WebBook: potassium iodide · chemical reference · https://webbook.nist.gov/cgi/cbook.cgi?ID=7681110

evidence_access

Primary abstract

experimental_model

Xenopus oocyte inside-out patches; construct species unresolved in accessed abstract.

limitations

Do not relabel the channel as a verified human isoform or infer a serum-potassium effect.

nutrient_topic

Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine

plain_language

Spermidine can limit outward potassium current.

primary_references

The mechanism of inward rectification of potassium channels: "long-pore plugging" by cytoplasmic polyamines. · 1995 · https://pubmed.ncbi.nlm.nih.gov/8648298/ · DOI 10.1085/jgp.106.5.923

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 430–436

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Xenopus oocyte inside-out patches; construct species unresolved in accessed abstract. · source_derived_draft · unverified_draft

## spermidine-kir-block Spermidine can limit outward potassium current. Cytoplasmic spermidine caused reversible voltage-dependent rectification of cloned HRK1 channels. Model: Xenopus oocyte inside-out patches; construct species unresolved in accessed abstract. Limitations: Do not relabel the channel as a verified human isoform or infer a serum-potassium effect. Evidence access: Primary abstract The mechanism of inward rectification of potassium channels: "long-pore plugging" by cytoplasmic polyamines. · 1995 · https://pubmed.ncbi.nlm.nih.gov/8648298/ · DOI 10.1085/jgp.106.5.923

evidence_access

Primary abstract

experimental_model

HRK1 patch-clamp comparison.

limitations

This is a gating comparison, not evidence that one nutrient replaces the other.

nutrient_topic

Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine

plain_language

Magnesium and spermidine influence the same channel with different kinetics.

primary_references

The mechanism of inward rectification of potassium channels: "long-pore plugging" by cytoplasmic polyamines. · 1995 · https://pubmed.ncbi.nlm.nih.gov/8648298/ · DOI 10.1085/jgp.106.5.923

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 438–444

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HRK1 patch-clamp comparison. · source_derived_draft · unverified_draft

## spermidine-kir-magnesium Magnesium and spermidine influence the same channel with different kinetics. Magnesium-associated unblock was almost instantaneous, whereas spermidine unblock was time dependent. Model: HRK1 patch-clamp comparison. Limitations: This is a gating comparison, not evidence that one nutrient replaces the other. Evidence access: Primary abstract The mechanism of inward rectification of potassium channels: "long-pore plugging" by cytoplasmic polyamines. · 1995 · https://pubmed.ncbi.nlm.nih.gov/8648298/ · DOI 10.1085/jgp.106.5.923

evidence_access

Primary full text

experimental_model

Rat pinealocytes and slices; electrogenic current assays.

limitations

Subtype assignment is pharmacological and supported by prior expression work, not a subtype-knockout demonstration.

nutrient_topic

D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate

plain_language

Transporting the amino acid can itself change the cell voltage.

primary_references

Glutamate transporter-mediated glutamate secretion in the mammalian pineal gland. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18945893/ · DOI 10.1523/JNEUROSCI.0894-08.2008

D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 152–158

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat pinealocytes and slices; electrogenic current assays. · source_derived_draft · unverified_draft

## d-aspartate-pineal-current Transporting the amino acid can itself change the cell voltage. D-aspartate elicited inward transporter-associated current in isolated rat pinealocytes; pharmacology favored GLT-1-type transport over ionotropic glutamate receptors. Model: Rat pinealocytes and slices; electrogenic current assays. Limitations: Subtype assignment is pharmacological and supported by prior expression work, not a subtype-knockout demonstration. Evidence access: Primary full text Glutamate transporter-mediated glutamate secretion in the mammalian pineal gland. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18945893/ · DOI 10.1523/JNEUROSCI.0894-08.2008

evidence_access

Primary full text

experimental_model

Mouse cortical terminals; 15 mM potassium stimulus, 10 micromolar TBOA.

limitations

This is evoked release under transporter blockade, not basal release in an intact human brain.

nutrient_topic

D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate

plain_language

Receptor-sensitive feedback changed release under an uptake-blocked assay condition.

primary_references

Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288

D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 232–238

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cortical terminals; 15 mM potassium stimulus, 10 micromolar TBOA. · source_derived_draft · unverified_draft

## d-aspartate-terminal-glutamate Receptor-sensitive feedback changed release under an uptake-blocked assay condition. D-aspartate at 10 micromolar enhanced potassium-evoked glutamate release in cortical synaptosomes superfused with TBOA; NMDA, AMPA/kainate and mGlu5 antagonists attenuated or prevented the effect. Model: Mouse cortical terminals; 15 mM potassium stimulus, 10 micromolar TBOA. Limitations: This is evoked release under transporter blockade, not basal release in an intact human brain. Evidence access: Primary full text Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28393897/ · DOI 10.1038/srep46288

evidence_access

Primary abstract

experimental_model

Bovine capillary RNA, membrane protein analysis and transport kinetics; aggregate apparent Km 14 micromolar at −61 mV.

limitations

The panel is not a physical three-protein complex; transport assays do not measure whole human brain exposure after food intake.

nutrient_topic

L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate

plain_language

The brain-facing barrier membrane participates in removing extracellular glutamate.

primary_references

Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10542215/ · DOI 10.1074/jbc.274.45.31891

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 106–112

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bovine capillary RNA, membrane protein analysis and transport kinetics; aggregate apparent Km 14 micromolar at −61 mV. · source_derived_draft · unverified_draft

## glutamate-bbb-clearance The brain-facing barrier membrane participates in removing extracellular glutamate. Bovine brain-capillary membrane preparations contained EAAT1/2/3 on the abluminal side and showed voltage- and potassium-dependent glutamate uptake. Model: Bovine capillary RNA, membrane protein analysis and transport kinetics; aggregate apparent Km 14 micromolar at −61 mV. Limitations: The panel is not a physical three-protein complex; transport assays do not measure whole human brain exposure after food intake. Evidence access: Primary abstract Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10542215/ · DOI 10.1074/jbc.274.45.31891

evidence_access

Primary abstract

experimental_model

Stimulated innate immune cells; both BHB enantiomers were active.

limitations

Not evidence that BHB corrects systemic potassium deficiency.

nutrient_topic

Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake

plain_language

A ketone altered an ion movement involved in inflammatory signaling.

primary_references

The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804

Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 368–374

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Stimulated innate immune cells; both BHB enantiomers were active. · source_derived_draft · unverified_draft

## fast-bhb-potassium A ketone altered an ion movement involved in inflammatory signaling. BHB prevented potassium efflux in the tested NLRP3 activation experiments. Model: Stimulated innate immune cells; both BHB enantiomers were active. Limitations: Not evidence that BHB corrects systemic potassium deficiency. Evidence access: Primary abstract The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804

evidence_access

Primary abstract

experimental_model

Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL.

limitations

Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial.

nutrient_topic

Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake

plain_language

Blood potassium and urinary loss changed together.

primary_references

The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996

Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 456–462

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. · source_derived_draft · unverified_draft

## fast-insulin-potassium Blood potassium and urinary loss changed together. Urinary potassium excretion fell from 66 to 21 microequivalents/min while plasma potassium also decreased. Model: Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. Limitations: Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial. Evidence access: Primary abstract The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/inositol-research/33875602.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d", "start_char": 0, "end_char": 1108, "text_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d"}

experimental_model

Genetic small-vessel disease mouse model and lipid rescue

exposure

PIP2 depletion and soluble PIP2 administration

limitations

Mouse disease model; not evidence that oral inositol treats human cerebrovascular disease.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Mus musculus

plain_language

The potassium channel can fail because its supporting lipid is missing, even though the channel protein remains.

primary_references

[ino-p33875602] PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity. (2021). https://pubmed.ncbi.nlm.nih.gov/33875602/ DOI: 10.1073/pnas.2025998118

tissue_or_cell_type

Brain capillary endothelium and cerebral circulation

trigger_kind

machinery_impairment Imported condition classification; unverified.

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1016–1027

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic small-vessel disease mouse model and lipid rescue · source_derived_draft · unverified_draft

### ino-kir-pip2 PIP2 depletion in the studied mouse small-vessel disease model impaired endothelial Kir2.1 activity. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The potassium channel can fail because its supporting lipid is missing, even though the channel protein remains. organism: Mus musculus tissue_or_cell_type: Brain capillary endothelium and cerebral circulation experimental_model: Genetic small-vessel disease mouse model and lipid rescue limitations: Mouse disease model; not evidence that oral inositol treats human cerebrovascular disease. exposure: PIP2 depletion and soluble PIP2 administration evidence_span: {"source_cache": "artifacts/inositol-research/33875602.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d", "start_char": 0, "end_char": 1108, "text_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d"} [ino-p33875602] PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity. (2021). https://pubmed.ncbi.nlm.nih.gov/33875602/ DOI: 10.1073/pnas.2025998118

evidence_span

{"source_cache": "artifacts/inositol-research/32787517.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3", "start_char": 0, "end_char": 1875, "text_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3"}

experimental_model

Arterial physiology, protein interactions and knockdown

exposure

SMIT1 manipulation, myo-inositol/raffinose and Kv7 blockade

limitations

Rat ex vivo arteries; not proof of a blood-pressure benefit from human inositol supplements.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Rattus norvegicus

plain_language

An inositol transporter can physically interact with a potassium-channel complex.

primary_references

[ino-p32787517] SMIT (Sodium-Myo-Inositol Transporter) 1 Regulates Arterial Contractility Through the Modulation of Vascular Kv7 Channels. (2020). https://pubmed.ncbi.nlm.nih.gov/32787517/ DOI: 10.1161/atvbaha.120.315096

tissue_or_cell_type

Renal and mesenteric arteries

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1042–1053

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Arterial physiology, protein interactions and knockdown · source_derived_draft · unverified_draft

### ino-smit1-kv7 Rat arterial SMIT1 associated with Kv7.4/Kv7.5 channels in the reported interaction experiments. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inositol transporter can physically interact with a potassium-channel complex. organism: Rattus norvegicus tissue_or_cell_type: Renal and mesenteric arteries experimental_model: Arterial physiology, protein interactions and knockdown limitations: Rat ex vivo arteries; not proof of a blood-pressure benefit from human inositol supplements. exposure: SMIT1 manipulation, myo-inositol/raffinose and Kv7 blockade evidence_span: {"source_cache": "artifacts/inositol-research/32787517.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3", "start_char": 0, "end_char": 1875, "text_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3"} [ino-p32787517] SMIT (Sodium-Myo-Inositol Transporter) 1 Regulates Arterial Contractility Through the Modulation of Vascular Kv7 Channels. (2020). https://pubmed.ncbi.nlm.nih.gov/32787517/ DOI: 10.1161/atvbaha.120.315096

evidence_access

Primary abstract

experimental_model

37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection.

limitations

The abstract did not report a significant potassium/creatinine ratio change; total output must not be confused with selective potassium wasting.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

Potassium output also changed in the short collection.

primary_references

Effects of dietary caffeine on renal handling of minerals in adult women. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2402180/ · DOI 10.1016/0024-3205(90)90616-y

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 332–338

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · 37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection. · source_derived_draft · unverified_draft

## caf-urine-k Potassium output also changed in the short collection. Total potassium output increased over the two-hour post-caffeine collection. Model: 37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection. Limitations: The abstract did not report a significant potassium/creatinine ratio change; total output must not be confused with selective potassium wasting. Evidence access: Primary abstract Effects of dietary caffeine on renal handling of minerals in adult women. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2402180/ · DOI 10.1016/0024-3205(90)90616-y

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/phosphorus-research/3860734.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf061281363419c0833fd3b160950e7f4c1a57ebeef46f3b73a0ad30f3b7f7e1", "start_char": 0, "end_char": 1400, "text_sha256": "cf061281363419c0833fd3b160950e7f4c1a57ebeef46f3b73a0ad30f3b7f7e1"}

experimental_model

Before/after phosphate correction with phrenic-nerve stimulation

exposure

Historical protocol: 10 mmol phosphorus as KH2PO4 infused over four hours

limitations

Small uncontrolled physiological experiment; potassium was also administered. Not a general infusion recommendation or proof of one intracellular mediator.

nutrient_topic

Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus

organism

Human

plain_language

Correcting the low phosphate measurement accompanied stronger diaphragm contractions in these patients.

primary_references

[phosphorus-p3860734] Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure. (1985). https://pubmed.ncbi.nlm.nih.gov/3860734/ DOI: 10.1056/nejm198508153130705

tissue_or_cell_type

Eight ventilated patients with acute respiratory failure

trigger_kind

biomarker_context Imported condition classification; unverified.

Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1050–1061

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Before/after phosphate correction with phrenic-nerve stimulation · source_derived_draft · unverified_draft

### phosphorus-diaphragm-rescue After serum phosphorus rose from 0.55 to 1.33 mmol/L, mean stimulated transdiaphragmatic pressure increased from 9.75 to 17.25 cm H2O. Condition category: biomarker_context nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting the low phosphate measurement accompanied stronger diaphragm contractions in these patients. organism: Human tissue_or_cell_type: Eight ventilated patients with acute respiratory failure experimental_model: Before/after phosphate correction with phrenic-nerve stimulation limitations: Small uncontrolled physiological experiment; potassium was also administered. Not a general infusion recommendation or proof of one intracellular mediator. exposure: Historical protocol: 10 mmol phosphorus as KH2PO4 infused over four hours evidence_span: {"source_cache": "artifacts/phosphorus-research/3860734.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf061281363419c0833fd3b160950e7f4c1a57ebeef46f3b73a0ad30f3b7f7e1", "start_char": 0, "end_char": 1400, "text_sha256": "cf061281363419c0833fd3b160950e7f4c1a57ebeef46f3b73a0ad30f3b7f7e1"} [phosphorus-p3860734] Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure. (1985). https://pubmed.ncbi.nlm.nih.gov/3860734/ DOI: 10.1056/nejm198508153130705