Actions of Ethanol on Voltage-Sensitive Sodium Channels: Effects on Neurotoxin Binding

摘要

Exposure of rat forebrain synaptosomes (P2) to ethanol in vitro reduced the specific binding of 3H batrachotoxinin A 20-alpha-benzoate (3Hbtx-B) to voltage-sensitive sodium channels. This effect of ethanol was concentration-dependent and was affected by the membrane potential. Under depolarizing conditions ethanol was significantly more potent at inhibiting 3Hbtx-B binding. Scatchard analysis of 3Hbtx-B binding revealed that ethanol increased the equilibrium binding constant without affecting the apparent maximum number of binding sites. The rate of formation of the 3Hbtx-B/receptor complex was unchanged in the presence of ethanol whereas the rate of dissociation was accelerated by ethanol. These findings are consistent with an indirect allosteric mechanism for inhibition of 3Hbtx-B binding. The binding of 3Hsaxitoxin was uneffected by ethanol suggesting that the specific receptor sites in the channel display differential sensitivity to the inhibitory effect of ethanol. These data, in conjunction with ion flux measurements, provide further evidence that ethanol can effect the voltage-sensitive sodium channels in neuronal membranes.