Volume-activated chloride currents from human fibroblasts: blockade by nimodipine.
The whole-cell patch clamp technique was used to identify and to characterize volume-activated Cl- current (ICl(vol)) in fibroblasts derived from human periodontal ligament. During osmotic cell swelling, the cells exhibited an outwardly rectifying current, which was dependent upon the concentration of external Cl-. The anion permeability sequence of the chloride channel for anions was as follows: SCN- > I- > Br- > Cl- > F- > methanesulphonate > gluconate. Being an inhibitor of Cl- channels and Cl-/HCO exchanger, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) inhibited the currents with a voltage-dependence (EC50 57 micromol/l at +80 mV), and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), a carboxylate analogue Cl- channel blocker, showed the reversible suppression of the currents in a dose-dependent manner (EC50 = 59 micromol/l). Nimodipine, a selective dihydropyridine Ca2+ channel blocker suppressed ICl(vol) (EC50 = 66 micromol/l) and the effects were quite similar to those of NPPB. Nifedipine, another DHP blocker also inhibited the currents but with lesser efficacy (EC50 = 139 micromol/l). The removal of external Ca2+ or the addition of Cd2+ in the bath solution did not affect the blocking effects of nimodipine on ICl(vol). These findings demonstrate that the human fibroblasts ICl(Vol) was suppressed by nimodipine in an extracellular Ca2+-independent way. These results may provide, at least in part, an explanation for the Ca2+-independent decrease in Cl-/organic osmolytes efflux and RVD responses by nimodipine in some cell types.
Chung
M K
MK
Department of Physiology, School of Dentistry and Institute of Oral Biology, Kyung Hee University, Seoul, Korea.
Kim
H Ch
HCh
D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D004553:Electric Conductivity; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D012680:Sensitivity and Specificity
D002121:Calcium Channel Blockers; D018118:Chloride Channels; D002712:Chlorides; D009553:Nimodipine; D002118:Calcium