FUNCTIONAL MODULATION OF HUMAN GANGLIONIC-LIKE NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTORS (NACHRS) BY L-TYPE CALCIUM-CHANNEL ANTAGONISTS

Recent studies suggest that the neuronal nicotinic acetylcholine receptors present on chromaffin cells contain a 1,4-dihydropyridine-sensitive site whose occupation blocks membrane depolarization (1). In the present study, several L-type Ca2+ channel blockers inhibited the activation of the nAChRs present in the human neuroblastoma cell line, IMR 32, in a dose-dependent manner with IC50 values ranging from 0.8-3 mu M. In contrast, omega-Conotoxin GVIA and omega-Agatoxin IVA had no effect up to 100 mu M. Furthermore, the inorganic channel blocker, cadmium, had no effect either alone or on the modulatory role of the L-type antagonists, suggesting that the effects of these agents on nAChRs are not mediated via an interaction with calcium channels but possibly via a direct interaction with the nAChR ionophore. (C) 1995 Academic Press, Inc.