Ethanol inhibition of L-type Ca2+ channels in PC12 cells: role of permeant ions.
The effects of acute ethanol exposure on voltage-activated Ca2+ channels in undifferentiated pheochromocytoma (PC12) cells were investigated using whole-cell patch clamp techniques. Concentrations of ethanol (5, 25 and 50 mM), at or below blood alcohol levels which constitute legal intoxication significantly reduced Ca2+ currents evoked from a holding potential of -30 mV. Ethanol-induced inhibition of current was voltage-dependent in some cases, but this was not consistently observed. Inhibition of currents was reversible and was not due to an osmotic effect. The non-inactivating nature of the current, the inhibition of the current by nifedipine, and the lack of inhibition by omega-conotoxin, indicated that the current was carried through high-voltage activated, L-type Ca2+ channels. Since intracellular Ca2+ levels were highly buffered by exchanged with the contents of the patch pipet, ethanol-induced inhibition of currents in PC12 cells is not likely to involve either a change in driving force due to a change in intracellular Ca2+ levels or potentiation of Ca(2+)-dependent Ca2+ channel inactivation by the influx of Ca2+. The degree of inhibition by 25 mM ethanol was the same when either Ca2+, Ba2+ or Na+ was used as the current-carrying ion. This equivalency suggest that the channel's ion selectivity filter is not a site of action for ethanol.
Mullikin-Kilpatrick
D
D
Department of Pharmacology, University of Massachusetts Medical Center, Worcester 01655.
Treistman
S N
SN
D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects; D016716:PC12 Cells; D012964:Sodium / Q000378:metabolism
D002121:Calcium Channel Blockers; D007473:Ion Channels; D001464:Barium; D000431:Ethanol; D012964:Sodium; D002118:Calcium