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Adenosine Triphosphate–dependent Asymmetry of Anion Permeation in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel

The cystic fibrosis transmembrane conductance regulator (CFTR) forms a tightly regulated channel that mediates the passive diffusion of Cl(−) ions. Here we show, using macroscopic current recording from excised membrane patches, that CFTR also shows significant, but highly asymmetrical, permeability...

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Detalles Bibliográficos
Autores principales: Linsdell, Paul, Hanrahan, John W.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217125/
https://www.ncbi.nlm.nih.gov/pubmed/9524141
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author Linsdell, Paul
Hanrahan, John W.
author_facet Linsdell, Paul
Hanrahan, John W.
author_sort Linsdell, Paul
collection PubMed
description The cystic fibrosis transmembrane conductance regulator (CFTR) forms a tightly regulated channel that mediates the passive diffusion of Cl(−) ions. Here we show, using macroscopic current recording from excised membrane patches, that CFTR also shows significant, but highly asymmetrical, permeability to a broad range of large organic anions. Thus, all large organic anions tested were permeant when present in the intracellular solution under biionic conditions (P (X)/P (Cl) = 0.048–0.25), whereas most were not measurably permeant when present in the extracellular solution. This asymmetry was not observed for smaller anions. ATPase inhibitors that “lock” CFTR channels in the open state (pyrophosphate, 5′-adenylylimidodiphosphate) disrupted the asymmetry of large anion permeation by allowing their influx from the extracellular solution, which suggests that ATP hydrolysis is required to maintain asymmetric permeability. The ability of CFTR to allow efflux of large organic anions represents a novel function of CFTR. Loss of this function may contribute to the pleiotropic symptoms seen in cystic fibrosis.
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spelling pubmed-22171252008-04-22 Adenosine Triphosphate–dependent Asymmetry of Anion Permeation in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Linsdell, Paul Hanrahan, John W. J Gen Physiol Article The cystic fibrosis transmembrane conductance regulator (CFTR) forms a tightly regulated channel that mediates the passive diffusion of Cl(−) ions. Here we show, using macroscopic current recording from excised membrane patches, that CFTR also shows significant, but highly asymmetrical, permeability to a broad range of large organic anions. Thus, all large organic anions tested were permeant when present in the intracellular solution under biionic conditions (P (X)/P (Cl) = 0.048–0.25), whereas most were not measurably permeant when present in the extracellular solution. This asymmetry was not observed for smaller anions. ATPase inhibitors that “lock” CFTR channels in the open state (pyrophosphate, 5′-adenylylimidodiphosphate) disrupted the asymmetry of large anion permeation by allowing their influx from the extracellular solution, which suggests that ATP hydrolysis is required to maintain asymmetric permeability. The ability of CFTR to allow efflux of large organic anions represents a novel function of CFTR. Loss of this function may contribute to the pleiotropic symptoms seen in cystic fibrosis. The Rockefeller University Press 1998-04-01 /pmc/articles/PMC2217125/ /pubmed/9524141 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Linsdell, Paul
Hanrahan, John W.
Adenosine Triphosphate–dependent Asymmetry of Anion Permeation in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel
title Adenosine Triphosphate–dependent Asymmetry of Anion Permeation in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel
title_full Adenosine Triphosphate–dependent Asymmetry of Anion Permeation in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel
title_fullStr Adenosine Triphosphate–dependent Asymmetry of Anion Permeation in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel
title_full_unstemmed Adenosine Triphosphate–dependent Asymmetry of Anion Permeation in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel
title_short Adenosine Triphosphate–dependent Asymmetry of Anion Permeation in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel
title_sort adenosine triphosphate–dependent asymmetry of anion permeation in the cystic fibrosis transmembrane conductance regulator chloride channel
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217125/
https://www.ncbi.nlm.nih.gov/pubmed/9524141
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