Effects of organic Ca antagonist, diltiazem, on neuromuscular transmission.

Abstract

The effects of the organic "Ca antagonist" diltiazem on the frog neuromuscular junction was investigated. The addition of diltiazem to the bath solution increased the frequency of spontaneous miniature endplate potentials (MEPPs) and quantal content. The amplitude of the endplate current (EPC) recorded from a d-tubocurarine-blocked endplate was significantly decreased by diltiazem (20-200 microM). However, the amplitude of miniature endplate current (MEPC) was relatively unchanged by diltiazem. The same degree of decrease in the decay time constant was observed in both EPC and MEPC. ACh potentials induced by repetitive iontophoresis were depressed gradually by low concentrations of diltiazem (2, 5 microM), suggesting enhanced desensitization. Using a patch-clamp method, the effects of diltiazem on ACh-activated single current in chick cultured myotubes were examined. The addition of diltiazem to the bath solution shortened the mean open time in a dose-dependent manner between 10 and 50 microM. The voltage-dependence of mean open time disappeared in the presence of diltiazem, with little change in the channel conductance. The present experiments suggest that diltiazem acts on the ACh-activated channel as an open channel blocker.