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This Article Full Text Full Text (PDF) All Versions of this Article: 91/1/149    most recent expphysiol.2005.031799v1 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Pusch, M Articles by Babini, E Search for Related Content PubMed PubMed Citation Articles by Pusch, M Articles by Babini, E Related Collections Genomic Physiology Symposia Papers

¹ Istituto di biofisica, CNR, Via De Marini 6, I-16149 Genova, Italy

Abstract

It was recently shown that the putative bacterial Cl^– channel, ClC-ec1, is in reality a Cl^––H⁺ antiporter. Our group has now shown that this is also the case for two human CLCs, ClC-4 and ClC-5. We found that the flux of Cl^– in one direction is stoichiometrically coupled to the movement of protons in the opposite direction, unveiling a behaviour that is typical of a transporter rather than a channel. This discovery will surely stimulate further research to elucidate the molecular elements responsible for the behaviour as a transporter. On the physiological level, the antiport activity of ClC-4/ClC-5 must lead to a review of the role of CLC proteins in intracellular compartments. Small organic molecules have been extremely useful tools for studying ion channels and many commercial drugs target specific ion channel proteins. Several blockers have been found to inhibit the plasma membrane-localized CLC channels ClC-0, ClC-1 and ClC-Ka. These compounds include 9-anthracene-carboxylic acid (9-AC), p-chlorophenoxy-propionic acid (CPP) and its derivatives, and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS). Two different binding sites have been identified, one extracellular and one intracellular. However, high-affinity ligands for most CLC proteins are still missing. Apart from being useful biophysical tools, such drugs may provide a way to modulate protein function in vivo. With these tasks to be accomplished, it is definitely an exciting time in the chloride transport field.

(Received 9 September 2005; accepted after revision 20 September 2005; first published online 22 September 2005)
Corresponding author Michael Pusch: Istituto di biofisica, CNR, Via De Marini 6, I-16149 Genova, Italy. Email: pusch{at}ge.ibf.cnr.it

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