CHOLINERGIC AGONISTS DECREASE QUANTAL OUTPUT AT THE FROG NEUROMUSCULAR-JUNCTION BY TARGETING A CALCIUM-CHANNEL BLOCKED BY OMEGA-CONOTOXIN

Nicotinic cholinergic agonists are known to decrease synchronous evoke d quantal output at the frog neuromuscular junction [Van der Kloot 199 3, J Physiol (Lond) 468:567-589]. Here we also show that carbachol dec reases the frequency of miniature endplate potentials (F-MEPP) in solu tions containing elevated levels of K+ and Ca2+. Carbachol did not dec rease F-MEPP in hypertonic solutions or in solutions containing the Ca 2+ ionophore ionomycin and Ca2+. We conclude that the nicotinic agonis ts decrease Ca2+ influx through voltage-gated Ca2+ channels. Carbachol did not alter two-pulse facilitation. A blocker of N-type Ca2+ channe ls, omega-conotoxin GVIA, antagonized the nicotinic agonist-induced de crease in evoked quantal output. The effect of carbachol was not alter ed by omega-conotoxin MVIIC, a blocker of P-type and certain other Ca( 2+)channels. The Ca2+ channel targeted by the nicotinic agonists appea rs to be of the N-type.