The inhibitory effects of nicotinic antagonists on currents elicited by GABA in rat hippocampal neurons

The nicotinic antagonists d-tubocurarine and trimethaphan camsylate competitively inhibit GABA-induced currents. Hexamethonium, mecamylamine and dihydro-β-erythroidine, other nicotinic antagonists, do not affect GABA-elicited currents. The trimethaphan effect is completely reversed by a putative convulsant receptor antagonist, α-isopropyl-α-methylγ-butyrolactone, which implies that the trimethaphan binding site may be closely associated with the convulsant site. However, nicotine was ineffective in competing for either the d-tubocurarine or trimethaphan effect at the GABA A receptor. From these observations, we proposed that the nicotinic and GABA A receptor ionophore complexes share similar configurational patterns that accomodate some of the same molecules. Possible mechanisms for the trimethaphan and d-tubocurarine blockades are discussed.