Component

Human cystic fibrosis transmembrane conductance regulator / CFTR

Human cystic fibrosis transmembrane conductance regulator / CFTR. Species, exposure and limitations are retained in each linked claim.

7 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. CFTR pore-region mutations changed anion selectivity, demonstrating that CFTR forms an anion channel.

    Human cystic fibrosis transmembrane conductance regulator / CFTR → Chloride ion source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/1712984.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b", "start_char": 0, "end_char": 849, "text_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b"}
    experimental_model
    CFTR expression and pore-residue mutagenesis
    exposure
    K95 or K335 substitutions
    limitations
    Selectivity experiment; not a supplementation study.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human CFTR in expression systems
    plain_language
    CFTR provides a route through which chloride can cross a membrane.
    primary_references
    [chloride-p1712984] Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. (1991). https://pubmed.ncbi.nlm.nih.gov/1712984/ DOI: 10.1126/science.1712984
    tissue_or_cell_type
    Cell plasma membrane

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 224–235

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

    ### chloride-cftr-channel CFTR pore-region mutations changed anion selectivity, demonstrating that CFTR forms an anion channel. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: CFTR provides a route through which chloride can cross a membrane. organism: Human CFTR in expression systems tissue_or_cell_type: Cell plasma membrane experimental_model: CFTR expression and pore-residue mutagenesis limitations: Selectivity experiment; not a supplementation study. exposure: K95 or K335 substitutions evidence_span: {"source_cache": "artifacts/chloride-research/1712984.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b", "start_char": 0, "end_char": 849, "text_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b"} [chloride-p1712984] Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. (1991). https://pubmed.ncbi.nlm.nih.gov/1712984/ DOI: 10.1126/science.1712984
    Complete structured claim and evidence

What acts on it

  1. PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal.

    Protein kinase A → Human cystic fibrosis transmembrane conductance regulator / CFTR source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/1716180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5", "start_char": 0, "end_char": 961, "text_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5"}
    experimental_model
    PKA phosphorylation and CFTR mutagenesis
    exposure
    Serines 660, 737, 795 and 813
    limitations
    Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human CFTR in cells
    plain_language
    A kinase switches the channel into a state that can respond to stimulation.
    primary_references
    [chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6
    tissue_or_cell_type
    CFTR regulatory domain

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 237–248

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

    ### chloride-pka-cftr PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase switches the channel into a state that can respond to stimulation. organism: Human CFTR in cells tissue_or_cell_type: CFTR regulatory domain experimental_model: PKA phosphorylation and CFTR mutagenesis limitations: Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model. exposure: Serines 660, 737, 795 and 813 evidence_span: {"source_cache": "artifacts/chloride-research/1716180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5", "start_char": 0, "end_char": 961, "text_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5"} [chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Pendrin knockdown did not change measured Calu-3 bicarbonate secretion.

    Human pendrin / SLC26A4 → Airway epithelial bicarbonate secretion source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/29536650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9da6a23e90b30ab4d0c2b537af65076e93cc3370470f64a9dafdeaaff525f157", "start_char": 0, "end_char": 1519, "text_sha256": "9da6a23e90b30ab4d0c2b537af65076e93cc3370470f64a9dafdeaaff525f157"}
    experimental_model
    Knockdown and epithelial secretion assays
    exposure
    Pendrin shRNA, CFTR deficiency, culture conditions
    limitations
    Authors explicitly limit extrapolation to other airway epithelia.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human Calu-3 cell line
    plain_language
    One airway model relied mainly on CFTR, despite detectable pendrin.
    primary_references
    [chloride-p29536650] Most bicarbonate secretion by Calu-3 cells is mediated by CFTR and independent of pendrin. (2018). https://pubmed.ncbi.nlm.nih.gov/29536650/ DOI: 10.14814/phy2.13641
    tissue_or_cell_type
    Airway gland-like epithelial model

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 1043–1054

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

    ### chloride-calu3-pendrin-null Pendrin knockdown did not change measured Calu-3 bicarbonate secretion. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: One airway model relied mainly on CFTR, despite detectable pendrin. organism: Human Calu-3 cell line tissue_or_cell_type: Airway gland-like epithelial model experimental_model: Knockdown and epithelial secretion assays limitations: Authors explicitly limit extrapolation to other airway epithelia. exposure: Pendrin shRNA, CFTR deficiency, culture conditions evidence_span: {"source_cache": "artifacts/chloride-research/29536650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9da6a23e90b30ab4d0c2b537af65076e93cc3370470f64a9dafdeaaff525f157", "start_char": 0, "end_char": 1519, "text_sha256": "9da6a23e90b30ab4d0c2b537af65076e93cc3370470f64a9dafdeaaff525f157"} [chloride-p29536650] Most bicarbonate secretion by Calu-3 cells is mediated by CFTR and independent of pendrin. (2018). https://pubmed.ncbi.nlm.nih.gov/29536650/ DOI: 10.14814/phy2.13641
    Complete structured claim and evidence

  2. Phosphorylated CFTR channels opened with ATP but not Mg-free ATP in this preparation.

    Magnesium-ATP complex → CFTR anion conductance source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/1718606.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67", "start_char": 0, "end_char": 925, "text_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67"}
    experimental_model
    Phosphorylated CFTR channel nucleotide assays
    exposure
    Hydrolyzable nucleotides, analogues and Mg-free ATP
    limitations
    Records the measured Mg/nucleotide dependence, not the paper’s historical assignment of opening to NBD1 hydrolysis.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human CFTR in expression preparations
    plain_language
    Magnesium and ATP are part of the working channel system; chloride alone is insufficient.
    primary_references
    [chloride-p1718606] Nucleoside triphosphates are required to open the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1718606/ DOI: 10.1016/0092-8674(91)90072-7
    tissue_or_cell_type
    Cytosolic channel face

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 250–261

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphorylated CFTR channel nucleotide assays · source_derived_draft · unverified_draft

    ### chloride-cftr-mgatp Phosphorylated CFTR channels opened with ATP but not Mg-free ATP in this preparation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium and ATP are part of the working channel system; chloride alone is insufficient. organism: Human CFTR in expression preparations tissue_or_cell_type: Cytosolic channel face experimental_model: Phosphorylated CFTR channel nucleotide assays limitations: Records the measured Mg/nucleotide dependence, not the paper’s historical assignment of opening to NBD1 hydrolysis. exposure: Hydrolyzable nucleotides, analogues and Mg-free ATP evidence_span: {"source_cache": "artifacts/chloride-research/1718606.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67", "start_char": 0, "end_char": 925, "text_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67"} [chloride-p1718606] Nucleoside triphosphates are required to open the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1718606/ DOI: 10.1016/0092-8674(91)90072-7
    Complete structured claim and evidence

  3. WNK1-mediated OSR1/SPAK activation increased CFTR bicarbonate permeability.

    Human WNK lysine deficient protein kinase 1 / WNK1 → CFTR bicarbonate permeability source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"}
    experimental_model
    Expression, duct-cell and pancreatic-tissue experiments
    exposure
    Low intracellular chloride; WNK1–OSR1/SPAK activation
    limitations
    Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human and guinea pig
    plain_language
    The channel became better at carrying bicarbonate for alkaline pancreatic fluid.
    primary_references
    [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
    tissue_or_cell_type
    Pancreatic duct

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 276–287

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression, duct-cell and pancreatic-tissue experiments · source_derived_draft · unverified_draft

    ### chloride-pancreatic-bicarbonate WNK1-mediated OSR1/SPAK activation increased CFTR bicarbonate permeability. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The channel became better at carrying bicarbonate for alkaline pancreatic fluid. organism: Human and guinea pig tissue_or_cell_type: Pancreatic duct experimental_model: Expression, duct-cell and pancreatic-tissue experiments limitations: Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency. exposure: Low intracellular chloride; WNK1–OSR1/SPAK activation evidence_span: {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"} [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
    Complete structured claim and evidence

  4. OSR1/SPAK activation inhibited CFTR-dependent chloride/bicarbonate exchange in the tested system.

    Oxidative stress responsive kinase 1 → Pancreatic CFTR-dependent chloride/bicarbonate exchange activity source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"}
    experimental_model
    Expression, duct-cell and pancreatic-tissue experiments
    exposure
    Low intracellular chloride; WNK1–OSR1/SPAK activation
    limitations
    Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human and guinea pig
    plain_language
    The same signaling program reduced an exchange route that could take bicarbonate back from the secretion.
    primary_references
    [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
    tissue_or_cell_type
    Pancreatic duct

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 289–300

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression, duct-cell and pancreatic-tissue experiments · source_derived_draft · unverified_draft

    ### chloride-pancreatic-exchange OSR1/SPAK activation inhibited CFTR-dependent chloride/bicarbonate exchange in the tested system. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same signaling program reduced an exchange route that could take bicarbonate back from the secretion. organism: Human and guinea pig tissue_or_cell_type: Pancreatic duct experimental_model: Expression, duct-cell and pancreatic-tissue experiments limitations: Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency. exposure: Low intracellular chloride; WNK1–OSR1/SPAK activation evidence_span: {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"} [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
    Complete structured claim and evidence

  5. Inducing pendrin approximately doubled the forskolin-stimulated CFTR-sensitive current in the tested cells.

    Human pendrin / SLC26A4 → CFTR anion conductance source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chloride-research/30742493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a", "start_char": 0, "end_char": 1882, "text_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a"}
    experimental_model
    Primary epithelial cultures and native tissue
    exposure
    IL-4 induction and pendrin knockdown
    limitations
    Inflamed surface epithelium differs from Calu-3; no universal airway assignment.
    nutrient_topic
    Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
    organism
    Human nasal and bronchial epithelia
    plain_language
    One transporter can influence another channel’s measured activity.
    primary_references
    [chloride-p30742493] Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia. (2019). https://pubmed.ncbi.nlm.nih.gov/30742493/ DOI: 10.1165/rcmb.2018-0158oc
    tissue_or_cell_type
    Ciliated airway surface

    Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 1069–1080

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary epithelial cultures and native tissue · source_derived_draft · unverified_draft

    ### chloride-surface-pendrin-cftr Inducing pendrin approximately doubled the forskolin-stimulated CFTR-sensitive current in the tested cells. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: One transporter can influence another channel’s measured activity. organism: Human nasal and bronchial epithelia tissue_or_cell_type: Ciliated airway surface experimental_model: Primary epithelial cultures and native tissue limitations: Inflamed surface epithelium differs from Calu-3; no universal airway assignment. exposure: IL-4 induction and pendrin knockdown evidence_span: {"source_cache": "artifacts/chloride-research/30742493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a", "start_char": 0, "end_char": 1882, "text_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a"} [chloride-p30742493] Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia. (2019). https://pubmed.ncbi.nlm.nih.gov/30742493/ DOI: 10.1165/rcmb.2018-0158oc
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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