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This Article Full Text Full Text (PDF) All Versions of this Article: 91/1/123    most recent expphysiol.2005.031757v1 Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Linsdell, P. Search for Related Content PubMed PubMed Citation Articles by Linsdell, P. Related Collections Symposia Papers GI & Epithelial

¹ Department of Physiology & Biophysics, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) functions as a Cl^– channel important in transepithelial salt and water transport. While there is a paucity of direct structural information on CFTR, much has been learned about the molecular determinants of the CFTR Cl^– channel pore region and the mechanism of Cl^– permeation through the pore from indirect structure–function studies. The first and sixth transmembrane regions of the CFTR protein play major roles in forming the channel pore and determining its functional properties by interacting with permeating Cl^– ions. Positively charged amino acid side-chains are involved in attracting negatively charged Cl^– ions into the pore region, where they interact briefly with a number of discrete sites on the pore walls. The pore appears able to accommodate more than one Cl^– ion at a time, and Cl^– ions bound inside the pore are probably sensitive to one another's presence. Repulsive interactions between Cl^– ions bound concurrently within the pore may be important in ensuring rapid movement of Cl^– ions through the pore. Chloride ion binding sites also interact with larger anions that can occlude the pore and block Cl^– permeation, thus inhibiting CFTR function. Other ions besides Cl^– are capable of passing through the pore, and specific amino acid residues that may be important in allowing the channel to discriminate between different anions have been identified. This brief review summarizes these mechanistic insights and tries to incorporate them into a simple cartoon model depicting the interactions between the channel and Cl^– ions that are important for ion translocation.

(Received 11 August 2005; accepted after revision 9 September 2005; first published online 12 September 2005)
Corresponding author P. Linsdell: Sir Charles Tupper Medical Building, 5850 College Street, Halifax, Nova Scotia B3H 1X5, Canada. Email: paul.linsdell{at}dal.ca