Department of Anesthesiology

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Channel or transporter? The CLC saga continues.

TitleChannel or transporter? The CLC saga continues.
Publication TypeJournal Article
Year of Publication2006
AuthorsPusch M, Zifarelli G, Murgia AR, Picollo A, Babini E
JournalExp Physiol
Volume91
Issue1
Pagination149-52
Date Published2006 Jan
ISSN0958-0670
Keywords2-Methyl-4-chlorophenoxyacetic Acid, Animals, Anthracenes, Antiporters, Binding Sites, Calcium Signaling, Chloride Channels, Chlorides, Humans, Ion Channel Gating, Membrane Transport Proteins, Multigene Family
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.

DOI10.1113/expphysiol.2005.031799
Alternate JournalExp. Physiol.
PubMed ID16179405
Grant ListGGP04018 / / Telethon / Italy