Inhibition of synaptosomal calcium uptake by ethanol

In vitro addition of ethanol or pentobarbital to synaptosomes isolated from rat or mouse brain inhibited the depolarization-dependent uptake of calcium without affecting uptake under nondepolarizing conditions. Ethanol inhibited the uptake in a concentration-dependent manner over the range of 45 to 720 mM. Analysis of the effects of ethanol and pentobarbital on calcium uptake at different temperatures indicated that the drugs did not change the activation energy of the process but shifted the Arrhenius curves toward higher temperatures. Synaptosomes isolated from mice chronically ingesting ethanol were found to be tolerant to the inhibitory effects of ethanol and pentobarbital but not tolerant to the inhibitory effects of acetaldehyde. Synaptosomes from ethanol tolerant-dependent mice accumulated less calcium in the absence of ethanol than did synaptosomes from control mice. This depression of uptake was reversed by in vitro exposure of the synaptosomes to a low concentration of ethanol, suggesting that it represents a biochemical response to withdrawal of alcohol. A single acute injection of ethanol 1 hr before sacrifice did not alter the calcium uptake activity or the drug sensitivity of the synaptosomes. These results suggest that the known inhibitory effects of ethanol and pentobarbital on the stimulated release of neurotransmitters and the development of tolerance of these effects may be mediated by the inhibition of the depolarization-dependent influx of calcium by these drugs.