HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 40, 41658-41663, October 1, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/40/41658    most recent M405517200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wright, A. M. Articles by Gray, M. A. Search for Related Content PubMed PubMed Citation Articles by Wright, A. M. Articles by Gray, M. A. Social Bookmarking                      What's this?

Novel Regulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channel Gating by External Chloride^*

Angela M. Wright, Xiandi Gong, Burns Verdon, Paul Linsdell, Anil Mehta¶, John R. Riordan||, Barry E. Argent, and Mike A. Gray**

From the Institute of Cell and Molecular Biosciences, University of Newcastle Upon Tyne, Framlington Place, Newcastle Upon Tyne, NE2 4HH, United Kingdom, Department of Physiology and Biophysics, Dalhousie University, Sir Charles Tupper Medical Building, Halifax, Nova Scotia, B3H 1X5, Canada, ^¶Division of Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, United Kingdom, and ^||Mayo Foundation, S. C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259

The cystic fibrosis transmembrane conductance regulator (CFTR) is vital for Cl^– and transport in many epithelia. As the concentration in epithelial secretions varies and can reach as high as 140 mM, the lumen-facing domains of CFTR are exposed to large reciprocal variations in Cl^– and levels. We have investigated whether changes in the extracellular anionic environment affects the activity of CFTR using the patch clamp technique. In fast whole cell current recordings, the replacement of 100 mM external Cl^– () with , Br^–, , or aspartate^– inhibited inward CFTR current (Cl^– efflux) by 50% in a reversible manner. Lowering alone by iso-osmotic replacement with mannitol also reduced Cl^– efflux to a similar extent. The maximal inhibition of CFTR current was 70%. Raising cytosolic calcium shifted the Cl^– dose-inhibition curve to the left but did not alter the maximal current inhibition observed. In contrast, a reduction in the internal [Cl^–] neither inhibited CFTR nor altered the block caused by reduced . Single channel recordings from outside-out patches showed that lowering markedly reduced channel open probability with little effect on unitary conductance. Together, these results indicate that alterations in alone and not the ratio regulate the gating of CFTR. Physiologically, our data have implications for current models of epithelial secretion and for the control of pH at epithelial cell surfaces.

Received for publication, May 18, 2004 , and in revised form, July 6, 2004.

^* This work was supported by a Wellcome Trust project grant (to M. A. G. and B. E. A.), a Canadian Institutes of Health research grant (to P. L.), and by a Wellcome Trust and CF Trust project grant (to A. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence should be addressed. Tel.: 44-191-222-7592; Fax: 44-191-222-6706; E-mail: m.a.gray{at}ncl.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Ishiguro, M. C. Steward, S. Naruse, S. B.H. Ko, H. Goto, R. M. Case, T. Kondo, and A. Yamamoto CFTR Functions as a Bicarbonate Channel in Pancreatic Duct Cells J. Gen. Physiol., March 1, 2009; 133(3): 315 - 326. [Abstract] [Full Text] [PDF]

				Z. Qu and H. C. Hartzell Bestrophin Cl- channels are highly permeable to HCO3- Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1371 - C1377. [Abstract] [Full Text] [PDF]

				T.-Y. Chen and T.-C. Hwang CLC-0 and CFTR: Chloride Channels Evolved From Transporters Physiol Rev, April 1, 2008; 88(2): 351 - 387. [Abstract] [Full Text] [PDF]

				M. R. Dorwart, N. Shcheynikov, Y. Wang, S. Stippec, and S. Muallem SLC26A9 is a Cl channel regulated by the WNK kinases J. Physiol., October 1, 2007; 584(1): 333 - 345. [Abstract] [Full Text] [PDF]

				M. N. Chernova, L. Jiang, D. J. Friedman, R. B. Darman, H. Lohi, J. Kere, D. H. Vandorpe, and S. L. Alper Functional Comparison of Mouse slc26a6 Anion Exchanger with Human SLC26A6 Polypeptide Variants: DIFFERENCES IN ANION SELECTIVITY, REGULATION, AND ELECTROGENICITY J. Biol. Chem., March 4, 2005; 280(9): 8564 - 8580. [Abstract] [Full Text] [PDF]