CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP

Erik M. Schwiebert; Marie E. Egan; Tae Ho Hwang; Stephanie B. Fulmer; Sandra S. Allen; Garry R. Cutting; William B. Guggino

doi:10.1016/S0092-8674(05)80011-X

CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP

Erik M. Schwiebert, Marie E. Egan, Tae Ho Hwang, Stephanie B. Fulmer, Sandra S. Allen, Garry R. Cutting, William B. Guggino

School of Medicine

Research output: Contribution to journal › Article › peer-review

573 Scopus citations

Abstract

The cystic fibrosis transmembrane conductance regulator(CFTR) functions to regulate both CI^- and Na⁺ conductive pathways; however, the cellular mechanisms whereby CFTR acts as a conductance regulator are unknown. CFTR and outwardly rectifying Cl^- channels (ORCCs) are distinct channels but are linked functionally via an unknown regulatory mechanism. We present results from whole-cell and single-channel patch-clamp recordings, short-circuit current recordings, and [γ-³²P]ATP release assays of normal, CF, and wild-type or mutant CFTR-transfected CF airway cultured epithelial cells wherein CFTR regulates ORCCs by triggering the transport of the potent agonist, ATP, out of the cell. Once released, ATP stimulates ORCCs through a P_2U purinergic receptor-dependent signaling mechanism. Our results suggest that CFTR functions to regulate other Cl^- secretory pathways in addition to itself conducting C^-.

Original language	English (US)
Pages (from-to)	1063-1073
Number of pages	11
Journal	Cell
Volume	81
Issue number	7
DOIs	https://doi.org/10.1016/S0092-8674(05)80011-X
State	Published - Jun 30 1995

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/S0092-8674(05)80011-X

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@article{0e36e918ec9e4ca79c2b7806023f268d,

title = "CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP",

abstract = "The cystic fibrosis transmembrane conductance regulator(CFTR) functions to regulate both CI- and Na+ conductive pathways; however, the cellular mechanisms whereby CFTR acts as a conductance regulator are unknown. CFTR and outwardly rectifying Cl- channels (ORCCs) are distinct channels but are linked functionally via an unknown regulatory mechanism. We present results from whole-cell and single-channel patch-clamp recordings, short-circuit current recordings, and [γ-32P]ATP release assays of normal, CF, and wild-type or mutant CFTR-transfected CF airway cultured epithelial cells wherein CFTR regulates ORCCs by triggering the transport of the potent agonist, ATP, out of the cell. Once released, ATP stimulates ORCCs through a P2U purinergic receptor-dependent signaling mechanism. Our results suggest that CFTR functions to regulate other Cl- secretory pathways in addition to itself conducting C-.",

author = "Schwiebert, {Erik M.} and Egan, {Marie E.} and Hwang, {Tae Ho} and Fulmer, {Stephanie B.} and Allen, {Sandra S.} and Cutting, {Garry R.} and Guggino, {William B.}",

note = "Funding Information: critical review of this manuscript, and Dr. Maloney for helping E. M. S. with developing the \[7-32P\]ATPr elease assay. This study was supported by National Institutes of Health and Cystic Fibrosis Foundation grants to W. B. G., National Institutes of Health and Cystic Fibrosis Foundation grants to M. E. E., a National Institutes of Health postdoctoral National Research Service Award to E. M. S., National Institutes of Health and Cystic Fibrosis Foundation grants to G. R. C., and Cystic Fibrosis Research Development Center and National Institutes of Health Specialized Centers of Research grants to the Johns Hopkins Cystic Fibrosis Group (W. B. G., director).",

year = "1995",

month = jun,

day = "30",

doi = "10.1016/S0092-8674(05)80011-X",

language = "English (US)",

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T1 - CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP

AU - Schwiebert, Erik M.

AU - Egan, Marie E.

AU - Hwang, Tae Ho

AU - Fulmer, Stephanie B.

AU - Allen, Sandra S.

AU - Cutting, Garry R.

AU - Guggino, William B.

N1 - Funding Information: critical review of this manuscript, and Dr. Maloney for helping E. M. S. with developing the \[7-32P\]ATPr elease assay. This study was supported by National Institutes of Health and Cystic Fibrosis Foundation grants to W. B. G., National Institutes of Health and Cystic Fibrosis Foundation grants to M. E. E., a National Institutes of Health postdoctoral National Research Service Award to E. M. S., National Institutes of Health and Cystic Fibrosis Foundation grants to G. R. C., and Cystic Fibrosis Research Development Center and National Institutes of Health Specialized Centers of Research grants to the Johns Hopkins Cystic Fibrosis Group (W. B. G., director).

PY - 1995/6/30

Y1 - 1995/6/30

N2 - The cystic fibrosis transmembrane conductance regulator(CFTR) functions to regulate both CI- and Na+ conductive pathways; however, the cellular mechanisms whereby CFTR acts as a conductance regulator are unknown. CFTR and outwardly rectifying Cl- channels (ORCCs) are distinct channels but are linked functionally via an unknown regulatory mechanism. We present results from whole-cell and single-channel patch-clamp recordings, short-circuit current recordings, and [γ-32P]ATP release assays of normal, CF, and wild-type or mutant CFTR-transfected CF airway cultured epithelial cells wherein CFTR regulates ORCCs by triggering the transport of the potent agonist, ATP, out of the cell. Once released, ATP stimulates ORCCs through a P2U purinergic receptor-dependent signaling mechanism. Our results suggest that CFTR functions to regulate other Cl- secretory pathways in addition to itself conducting C-.

AB - The cystic fibrosis transmembrane conductance regulator(CFTR) functions to regulate both CI- and Na+ conductive pathways; however, the cellular mechanisms whereby CFTR acts as a conductance regulator are unknown. CFTR and outwardly rectifying Cl- channels (ORCCs) are distinct channels but are linked functionally via an unknown regulatory mechanism. We present results from whole-cell and single-channel patch-clamp recordings, short-circuit current recordings, and [γ-32P]ATP release assays of normal, CF, and wild-type or mutant CFTR-transfected CF airway cultured epithelial cells wherein CFTR regulates ORCCs by triggering the transport of the potent agonist, ATP, out of the cell. Once released, ATP stimulates ORCCs through a P2U purinergic receptor-dependent signaling mechanism. Our results suggest that CFTR functions to regulate other Cl- secretory pathways in addition to itself conducting C-.

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CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP

Abstract

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