THE INHIBITORY EFFECTS OF NICOTINIC ANTAGONISTS ON CURRENTS ELICITED BY GABA IN RAT HIPPOCAMPAL-NEURONS

The nicotinic antagonists d-tubocurarine and trimethaphan camsylate co mpetitively inhibit GABA-induced currents. Hexamethonium, mecamylamine and dihydro-beta-erythroidine, other nicotinic antagonists, do not af fect GABA-elicited currents. The trimethaphan effect is completely rev ersed by a putative convulsant receptor antagonist, alpha-isopropyl-al pha-methyl-gamma-butyrolactone, which implies that the trimethaphan bi nding 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 GAB(A), receptor. From these observation s, we propose that the nicotinic and GAB(A), receptor ionophore comple xes share similar configurational patterns that accommodate some of th e same molecules. Possible mechanisms for the trimethaphan and d-tuboc urarine blockades are discussed.