Extracellular acidification elicits a chloride current that shares characteristics with ICl(swell).
A Cl- current activated by extracellular acidification, ICl(pHac), 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 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. 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 time- and voltage-dependent inactivation observed for ICl(swell); and 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) that, additionally, alters the biophysical properties of the channel.
Medical Research Council, Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, London, United Kingdom. m.nobles@ucl.ac.uk
Muriel
M
Nobles
Christopher F
CF
Higgins
Alessandro
A
Sardini
D002460:Cell Line; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D045604:Extracellular Fluid / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D015398:Signal Transduction / Q000502:physiology*
D018118:Chloride Channels; D002712:Chlorides