Inhibitory action of nicotinic antagonists on transmitter release at the neuromuscular junction of the rat

Abstract

The effects of two nicotinic antagonists, d-tubocurarine (TC) and hexamethonium (HEX) were tested on the rat diaphragm neuromuscular junction during train-of-six stimuli to determine if a second action of these antagonists on evoked release could be demonstrated, in addition to its known impact of blocking the autoreceptor pathway. To minimize the autoreceptor pathway, the preparations were examined under low transmitter release conditions. It was observed that both compounds significantly depressed the end-plate potential amplitudes more than the miniature end-plate potential amplitudes, while also significantly depressing quantal release output. This inhibitory action is contrary to what is observed when transmitter release is high, where feedback regulation via the autoreceptors serves a prominent role. It is concluded that this depressive action on transmitter output contributes to onset of tetanic fade and that when higher concentrations of these antagonists are used this inhibitory action of TC and HEX may override autoreceptor feedback regulation.