Abstract

Exposure of rat forebrain synaptosomes (P2) to ethanol in vitro reduced the specific binding of [3H]batrachotoxinin A 20-alpha-benzoate ([3H]BTX-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 [3H]BTX-B binding. Scatchard analysis of [3H]BTX-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 [3H]BTX-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 [3H]BTX-B binding. The binding of [3H]saxitoxin was unaffected 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 affect the voltage-sensitive sodium channels in neuronal membranes.