Ethanol-induced reduction of neuronal calcium currents in Aplysia: an examination of possible mechanisms.
1. Experiments were performed to determine the mechanisms by which ethanol (EtOH) decreases the amplitude of voltage-dependent inward currents through calcium channels in Aplysia neurons. Voltage-clamp protocols used conditioning prepulses of varying amplitude, duration, and frequency, to examine the relationship between prior activity of the channel and EtOH action. Calcium and barium were used as charge carriers, allowing dissociation of effects due to inactivation of calcium channels from other perturbations resulting in the impediment of current flow through the open channel. 2. When Ba2+ was the charge carrier and channel activation was unconfounded by inactivation processes, the reduction of ICa produced by EtOH was independent of the voltage, frequency, or duration of conditioning prepulses. 3. When Ca2+ was the charge carrier, ICa was reduced as a function of conditioning prepulses, in three protocols used. EtOH enhanced this reduction, most probably because of its effects on the inactivation of ICa. Consistent with this interpretation, the time constant of decay of ICa was decreased, and recovery from inactivation was retarded by EtOH. 4. EtOH did not reduce ICa by a change in membrane surface potential, at least at low EtOH concentrations. 5. An analysis of the time course of development of ICa reduction by EtOH showed that it developed slowly, over a matter of minutes. 6. Our data indicate that EtOH does not reduce ICa by direct occlusion of the calcium channel. EtOH affects the inactivation of the calcium current, and this may occur by an action on the channel protein.
D000818:Animals; D001048:Aplysia; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*
D001464:Barium; D000431:Ethanol; D002118:Calcium