PMID: 9524141May 2, 1998Paper

Adenosine triphosphate-dependent asymmetry of anion permeation in the cystic fibrosis transmembrane conductance regulator chloride channel

The Journal of General Physiology
Paul Linsdell, J W Hanrahan

Abstract

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 (PX/PCl = 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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Citations

Nov 12, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·F GuizzardiG Meyer
Apr 22, 2009·The Journal of Membrane Biology·Mohammad Fatehi, Paul Linsdell
Jul 29, 2011·The Journal of Membrane Biology·Ryan G HolsteadPaul Linsdell
May 2, 2008·Pflügers Archiv : European journal of physiology·Jing-Jun ZhouPaul Linsdell
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Nov 2, 2002·British Journal of Pharmacology·Xiandi GongPaul Linsdell
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Nov 12, 2003·The Journal of General Physiology·Xiandi Gong, Paul Linsdell
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Jan 19, 2016·Biochimica Et Biophysica Acta·Paul Linsdell
Dec 18, 2013·Molecular Membrane Biology·Paul Linsdell
Apr 8, 2003·The Journal of Physiology·Xiandi Gong, Paul Linsdell
Apr 3, 2007·European Journal of Pharmacology·Jing-Jun Zhou, Paul Linsdell
Oct 9, 2015·Biophysical Journal·Niraj ModiUlrich Kleinekathöfer
May 23, 2012·British Journal of Pharmacology·Man-Song LiPaul Linsdell

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