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

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Abstract
A Cl− current activated by extracellular acidification, I Cl(pHac), has been characterized in various mammalian cell types. Many of the properties of I Cl(pHac) are similar to those of the cell swelling-activated Cl− current I Cl(swell): ion selectivity (I− > Br− > Cl− > F−), pharmacology [ I Cl(pHac) is inhibited by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS), 1,9-dideoxyforskolin (DDFSK), diphenylamine-2-carboxylic acid (DPC), and niflumic acid], lack of dependence on intra- or extracellular Ca2+, and presence in all cell types tested. I Cl(pHac) differs from I Cl(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 time- and voltage-dependent inactivation observed for I Cl(swell); and 3 ) it shows a more pronounced outward rectification. Despite these differences, study of the transition between the two currents strongly suggests that I Cl(swell) and I Cl(pHac) are related and that extracellular acidification reflects a novel stimulus for activating I Cl(swell) that, additionally, alters the biophysical properties of the channel.