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Alcohol Inhibits the Depolarization‐Induced Stimulation of Oxidative Phosphorylation in Synaptosomes
Author(s) -
Li Hong Lan,
Wu Shaolong,
Rottenberg Hagai
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66041691.x
Subject(s) - veratridine , depolarization , stimulation , chemistry , ionomycin , ruthenium red , protonophore , synaptosome , oxidative phosphorylation , membrane potential , verapamil , biophysics , medicine , pharmacology , biochemistry , endocrinology , calcium , biology , sodium channel , sodium , membrane , organic chemistry
The effects of alcohol and Ca 2+ transport inhibitors on depolarization‐induced stimulation of oxidative phosphorylation and free‐Ca 2+ concentrations in rat synaptosomes were investigated. Glucose oxidation was stimulated by depolarization with K + or veratridine and by the Ca 2+ ionophore ionomycin. The stimulation by K + , veratridine, and ionomycin was correlated with elevation of synaptosomal free Ca 2+ . Depolarization‐stimulated respiration was inhibited by verapamil, Cd 2+ , and ruthenium red but not by diltiazem. Synaptosomal Ca 2+ elevation was inhibited by verapamil but not by ruthenium red. These results indicate that the stimulation depends on elevation of mitochondrial free Ca 2+ . Ethanol, at pharmacological concentrations (50–200 m M ), inhibited the Ca 2+ ‐dependent stimulation of oxidative phosphorylation. This inhibition resulted, in part, from the inhibition of voltage‐gated Ca 2+ channels, which inhibited the elevation of synaptosomal free Ca 2+ , and, in part, from the stimulation of the mitochondrial Ca 2+ /Na + antiporter, which inhibited the elevation of the mitochondrial matrix free Ca 2+ . The inhibition by ethanol of the excitation‐induced stimulation of oxidative phosphorylation in the synapse may contribute to the depressant and narcotic effects of alcohol and enhance excitotoxicity.