Alcohols and synaptosomal calcium transport

Abstract

Synaptosomes were isolated from rat and mouse brain and the effects of alcohol addition on calcium uptake were studied in vitro. Ethanol inhibited potassium-, glutamate-, and veratridine-stimulated calcium uptake. The inhibitory effects were obtained with concentrations of ethanol (less than or equal to 100 mM) which did not alter synaptosomal membrane potentials. Elevation of extrasynaptosomal calcium reduced the inhibitory effect of ethanol, resulting in apparently competitive kinetics. The inhibitory potencies of a series of alkanols were correlated with their membrane/buffer partition coefficients, implicating hydrophobic regions of the membrane as the site of alcohol action. However, not all nerve endings were equally sensitive to ethanol. Inhibition of potassium-stimulated calcium uptake was greater with synaptosomes prepared from cerebellum and striatum than with preparations from cortex or brain stem. In contrast, veratridine-stimulated calcium uptake (which is dependent upon sodium influx) was inhibited more strongly in cortex than in cerebellum. These results suggest that the calcium channels in cerebellum are more sensitive to ethanol than the calcium channels in cortex, whereas sodium channels in cortex are more sensitive than those in cerebellum.