Epithelial sodium channel

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

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

The sodium entry channel itself can fail.

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 928–939

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-current The alpha- or beta-subunit variants identified in affected families caused loss of channel activity. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sodium entry channel itself can fail. 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

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

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

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> sodium -> potassium

experimental_model

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

limitations

Cleaved subunits and amiloride response support ENaC inhibition; the molecular cause was unresolved.

nutrient_topic

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

organism

Mus musculus

plain_language

With less dietary Mg, these kidneys reduced the sodium entry pathway that normally helps drive potassium secretion.

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 154–164

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-restriction-reduces-enac-activity Mg restriction reduced cleaved alpha/gamma ENaC abundance and blunted amiloride-induced sodium excretion in mice. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: With less dietary Mg, these kidneys reduced the sodium entry pathway that normally helps drive potassium secretion. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Cleaved subunits and amiloride response support ENaC inhibition; the molecular cause was unresolved. 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

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

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

Model-specific non-sufficiency; not a claim that isolated Mg restriction can never lower K at other durations or in humans.

nutrient_topic

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

organism

Mus musculus

plain_language

A low Mg blood value alone did not guarantee falling potassium: sodium transport and the rest of the kidney response mattered.

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 166–176

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-restriction-alone-not-sufficient-hypokalemia Isolated Mg restriction produced hypomagnesemia without the hypokalemia observed under combined Na/Mg restriction in the tested mice. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low Mg blood value alone did not guarantee falling potassium: sodium transport and the rest of the kidney response mattered. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Model-specific non-sufficiency; not a claim that isolated Mg restriction can never lower K at other durations or in humans. 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

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/8524790.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "31f8bb4c6f32108b9d6042db6ec60ed8c77b21af322621a2cb0fd9c2aa7236a1", "start_char": 0, "end_char": 1598, "text_sha256": "31f8bb4c6f32108b9d6042db6ec60ed8c77b21af322621a2cb0fd9c2aa7236a1"}

experimental_model

Human kindred analysis and oocyte channel-expression comparison

exposure

P616L as numbered in the paper

limitations

Gain-of-function genetic disease; no implication that this mutation is caused by salt intake.

nutrient_topic

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

organism

Human variant in Xenopus oocytes

plain_language

A mutation can make sodium entry excessive even without a defective sodium supply.

primary_references

[sodium-p8524790] A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. (1995). https://pubmed.ncbi.nlm.nih.gov/8524790/ DOI: 10.1073/pnas.92.25.11495

tissue_or_cell_type

ENaC beta-subunit regulatory tail

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 954–965

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human kindred analysis and oocyte channel-expression comparison · source_derived_draft · unverified_draft

### sodium-liddle-current The beta-subunit P616L mutant increased amiloride-sensitive sodium current 8.8-fold versus normal subunits in oocytes. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mutation can make sodium entry excessive even without a defective sodium supply. organism: Human variant in Xenopus oocytes tissue_or_cell_type: ENaC beta-subunit regulatory tail experimental_model: Human kindred analysis and oocyte channel-expression comparison limitations: Gain-of-function genetic disease; no implication that this mutation is caused by salt intake. exposure: P616L as numbered in the paper evidence_span: {"source_cache": "artifacts/sodium-research/8524790.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "31f8bb4c6f32108b9d6042db6ec60ed8c77b21af322621a2cb0fd9c2aa7236a1", "start_char": 0, "end_char": 1598, "text_sha256": "31f8bb4c6f32108b9d6042db6ec60ed8c77b21af322621a2cb0fd9c2aa7236a1"} [sodium-p8524790] A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. (1995). https://pubmed.ncbi.nlm.nih.gov/8524790/ DOI: 10.1073/pnas.92.25.11495

evidence_span

{"source_cache": "artifacts/sodium-research/10358046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d53e3e8ce41bb21d5cac2a5bfe6a6abdc702d0870add9c0a002e58ac374a97b", "start_char": 0, "end_char": 1343, "text_sha256": "7d53e3e8ce41bb21d5cac2a5bfe6a6abdc702d0870add9c0a002e58ac374a97b"}

experimental_model

Immediate-early gene induction and channel coexpression

exposure

Aldosterone exposure; receptor dependence and protein-synthesis tests

limitations

Cell and oocyte mechanism; the study does not imply that dietary sodium directly activates SGK1 in every tissue.

nutrient_topic

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

organism

Rabbit/mouse collecting-duct preparations; mouse SGK in Xenopus oocytes

plain_language

The kinase can increase sodium flow through ENaC.

primary_references

[sodium-p10358046] sgk is an aldosterone-induced kinase in the renal collecting duct. Effects on epithelial na+ channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10358046/ DOI: 10.1074/jbc.274.24.16973

tissue_or_cell_type

Cortical collecting duct and expression system

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 408–419

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immediate-early gene induction and channel coexpression · source_derived_draft · unverified_draft

### sodium-sgk-enac Coexpression of mouse sgk with the three ENaC subunits increased sodium current in Xenopus oocytes. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kinase can increase sodium flow through ENaC. organism: Rabbit/mouse collecting-duct preparations; mouse SGK in Xenopus oocytes tissue_or_cell_type: Cortical collecting duct and expression system experimental_model: Immediate-early gene induction and channel coexpression limitations: Cell and oocyte mechanism; the study does not imply that dietary sodium directly activates SGK1 in every tissue. exposure: Aldosterone exposure; receptor dependence and protein-synthesis tests evidence_span: {"source_cache": "artifacts/sodium-research/10358046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d53e3e8ce41bb21d5cac2a5bfe6a6abdc702d0870add9c0a002e58ac374a97b", "start_char": 0, "end_char": 1343, "text_sha256": "7d53e3e8ce41bb21d5cac2a5bfe6a6abdc702d0870add9c0a002e58ac374a97b"} [sodium-p10358046] sgk is an aldosterone-induced kinase in the renal collecting duct. Effects on epithelial na+ channels. (1999). https://pubmed.ncbi.nlm.nih.gov/10358046/ DOI: 10.1074/jbc.274.24.16973

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

Higher sodium-channel availability can support the secretory machinery used for K balance.

evidence_location

Figures 3-5; interaction and anti-FLAG surface-labeling experiments.

experimental_model

Oocyte binding, current and surface-labeling assays

limitations

Molecular sufficiency does not establish exclusive control in intact kidneys.

nutrient_topic

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

organism

Xenopus laevis

plain_language

Phosphorylation weakens the sodium-channel removal signal, leaving more channels at the surface.

primary_references

[debonneville-2001-sgk-nedd4] Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression (2001). https://pubmed.ncbi.nlm.nih.gov/11742982/ DOI: 10.1093/emboj/20.24.7052

tissue_or_cell_type

Oocytes

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 421–432

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oocyte binding, current and surface-labeling assays · source_derived_draft · unverified_draft

### renal-phospho-nedd4l-releases-enac SGK-dependent Nedd4-2 phosphorylation reduced its ENaC interaction and increased ENaC surface expression in oocytes. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphorylation weakens the sodium-channel removal signal, leaving more channels at the surface. organism: Xenopus laevis tissue_or_cell_type: Oocytes experimental_model: Oocyte binding, current and surface-labeling assays limitations: Molecular sufficiency does not establish exclusive control in intact kidneys. cross_nutrient: Higher sodium-channel availability can support the secretory machinery used for K balance. evidence_location: Figures 3-5; interaction and anti-FLAG surface-labeling experiments. [debonneville-2001-sgk-nedd4] Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression (2001). https://pubmed.ncbi.nlm.nih.gov/11742982/ DOI: 10.1093/emboj/20.24.7052

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Impaired ENaC sodium-channel adaptation accompanies defective K clearance.

evidence_location

Results Figure 2; two-day versus five-day dietary comparison.

experimental_model

Inducible tubular deletion; two-day high-K citrate diet

limitations

Excretion approached controls after longer adaptation; ROMK apical localization increased rather than decreased.

nutrient_topic

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

organism

Mus musculus

plain_language

Removing kidney SGK1 impairs the initial ability to clear a potassium load.

primary_references

[al-qusairi-2016-renal-sgk1] Renal tubular SGK1 deficiency causes impaired K+ excretion via loss of regulation of NEDD4-2/WNK1 and ENaC (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5005279/ DOI: 10.1152/ajprenal.00002.2016

tissue_or_cell_type

Kidney tubules

trigger_kind

machinery_impairment Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 434–445

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible tubular deletion; two-day high-K citrate diet · source_derived_draft · unverified_draft

### renal-sgk1-loss-impairs-high-k-excretion Renal Sgk1 deletion blunted the early increase in urinary K excretion on high-K feeding, with hyperkalemia and reduced ENaC processing. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing kidney SGK1 impairs the initial ability to clear a potassium load. organism: Mus musculus tissue_or_cell_type: Kidney tubules experimental_model: Inducible tubular deletion; two-day high-K citrate diet limitations: Excretion approached controls after longer adaptation; ROMK apical localization increased rather than decreased. cross_nutrient: Impaired ENaC sodium-channel adaptation accompanies defective K clearance. evidence_location: Results Figure 2; two-day versus five-day dietary comparison. [al-qusairi-2016-renal-sgk1] Renal tubular SGK1 deficiency causes impaired K+ excretion via loss of regulation of NEDD4-2/WNK1 and ENaC (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5005279/ DOI: 10.1152/ajprenal.00002.2016

cross_nutrient

This biochemical sodium-channel pathway contributes to the machinery for K handling.

evidence_location

Figure 2.

experimental_model

Expression, kinase-dead and site-mutant experiments

limitations

Residue numbers are construct/species-specific; nutritional K sensing was not tested.

nutrient_topic

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

organism

Xenopus laevis

plain_language

SGK1 modifies the protein that normally restrains sodium channels.

primary_references

[debonneville-2001-sgk-nedd4] Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression (2001). https://pubmed.ncbi.nlm.nih.gov/11742982/ DOI: 10.1093/emboj/20.24.7052

tissue_or_cell_type

Oocytes

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 408–419

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression, kinase-dead and site-mutant experiments · source_derived_draft · unverified_draft

### renal-sgk1-phosphorylates-nedd4l Sgk1 phosphorylated Nedd4-2 at Ser444 and less strongly Ser338 in Xenopus constructs. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: SGK1 modifies the protein that normally restrains sodium channels. organism: Xenopus laevis tissue_or_cell_type: Oocytes experimental_model: Expression, kinase-dead and site-mutant experiments limitations: Residue numbers are construct/species-specific; nutritional K sensing was not tested. cross_nutrient: This biochemical sodium-channel pathway contributes to the machinery for K handling. evidence_location: Figure 2. [debonneville-2001-sgk-nedd4] Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression (2001). https://pubmed.ncbi.nlm.nih.gov/11742982/ DOI: 10.1093/emboj/20.24.7052