Recent developments in alcoholism:neuronal ion channels.

Effects of ethanol on ion channels were last reviewed in this series in 1987; since that time our understanding of ion channel function has advanced markedly and this explosion of knowledge has also strongly influenced studies of ethanol actions. In particular, it is now clear that there are many subtypes of ligand- and voltage-gated ion channels and that the ethanol sensitivity of these channels is subtype dependent. Among the ligand-gated ion channels, the glutamate-activated channels, particularly the NMDA subtypes, are inhibited by low concentrations of ethanol. In contrast, function of 5-HT3- and some GABA-activated channels is enhanced by acute ethanol exposure. In addition, certain voltage-dependent calcium channels are potently inhibited by ethanol. With chronic exposure, there are often compensatory changes in ion channel function that may play a role in tolerance or dependence. Genetic approaches, both classical and molecular, have proven powerful in understanding the role of ion channels in ethanol actions and are likely to figure prominently in future research in this area.