ALCOHOL INHIBITS THE DEPOLARIZATION-INDUCED STIMULATION OF OXIDATIVE-PHOSPHORYLATION IN SYNAPTOSOMES

The effects of alcohol and Ca2+ transport inhibitors on depolarization -induced stimulation of oxidative phosphorylation and free-Ca2+ concen trations in rat synaptosomes were investigated. Glucose oxidation was stimulated by depolarization with K+ or veratridine and by the Ca2+ io nophore ionomycin. The stimulation by K+, veratridine, and ionomycin w as correlated with elevation of synaptosomal free Ca2+. Depolarization -stimulated respiration was inhibited by verapamil, Cd2+, and rutheniu m red but not by diltiazem. Synaptosomal Ca2+ elevation was inhibited by verapamil but not by ruthenium red. These results indicate that the stimulation depends on elevation of mitochondrial free Ca2+. Ethanol, at pharmacological concentrations (50-200 mM), inhibited the Ca2+-dep endent stimulation of oxidative phosphorylation. This inhibition resul ted, in part, from the inhibition of voltage-gated Ca2+ channels, whic h inhibited the elevation of synaptosomal free Ca2+, and, in part, fro m the stimulation of the mitochondrial Ca2+/Na+ antiporter, which inhi bited the elevation of the mitochondrial matrix free Ca2+. The inhibit ion by ethanol of the excitation-induced stimulation of oxidative phos phorylation in the synapse may contribute to the depressant and narcot ic effects of alcohol and enhance excitotoxicity.