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Am J Physiol Cell Physiol (August 11, 2004). doi:10.1152/ajpcell.00549.2002
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Submitted on November 25, 2002
Accepted on July 15, 2004

Extracellular acidification elicits a chloride current that shares characteristics with ICl(swell)

Muriel Nobles1*, Christopher F Higgins1, and Alessandro Sardini1

1 Clinical Sciences Centre, Medical Research Council, London, United Kingdom

* To whom correspondence should be addressed. E-mail: m.nobles{at}ucl.ac.uk.

A chloride current,ICl(pHac), activated by extracellular acidification, has been characterized in various mammalian cell types. Many of the properties of ICl(pHac) are similar to those of the cell swelling-activated Cl- current ICl(swell): ion selectivity (I->Br->Cl->F-), pharmacology (ICl(pHac) is inhibited by DIDS, DDFSK, DPC, and niflumic acid), lack of dependency on intra- or extracellular Ca2+ ions, and presence in all cell types tested. ICl(pHac) differs from ICl(swell) in three aspects: 1. its rate of activation and inactivation is very much more rapid, currents reaching a maximum in seconds rather than minutes; 2. it exhibits a slow voltage-dependent activation in contrast to the fast voltage-dependent activation and voltage-dependent inactivation observed for ICl(swell); 3. it shows a more pronounced outward rectification. Despite these differences, study of the transition between the two currents strongly suggests that ICl(swell) and ICl(pHac) are related and that extracellular acidification reflects a novel stimulus for activating ICl(swell) which, additionally, alters the biophysical properties of the channel.




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