Effect of an homologous series of aliphatic alcohols on neuronal and smooth muscle voltage-dependent Ca²⁺ channels

The acute inhibitory actions of alcohol on K⁺-stimulated ⁴⁵Ca²⁺ uptake into synaptosomes shows regional variation in sensitivity throughout the brain, suggesting the possibility of a selective action on a specific Ca²⁺ channel subtype. This was examined by comparing the effects of a homologous series of aliphatic alcohols on synaptosomal Ca²⁺ channels with their actions on K⁺-stimulated Ca²⁺ channels in guinea-pig intestinal longitudinal muscle, which have been demonstrated to be of the L-type. K⁺-stimulated contraction of and [³H]nitrendipine binding to smooth muscle were both inhibited by the alcohols at similar concentrations, with the potency increasing with chain length. In synaptosomes, however, K⁺-stimulated ⁴⁵Ca²⁺ uptake was 5-30 times more sensitive to the inhibitory actions of alcohol than were [³H]nitrendipine and [¹²⁵I]ω-conotoxin binding. These observations suggest that K⁺-stimulated ⁴⁵Ca²⁺ uptake is mediated by a non-L non-N type channel which is more sensitive to the acute effects of alcohols. This is supported by the observation that K⁺-stimulated ⁴⁵Ca²⁺ uptake which is insensitive to L-and N-channel antagonists was inhibited by funnel web spider venom.