ABSTRACT
Effects of trimetaphan have been tested on locust retractor unguis and extensor tibiae nerve–muscle preparations. Trimetaphan reversibly reduced the neurally evoked twitch amplitude of the retractor unguis muscle, dependent upon dose and partly upon stimulus frequency. Contractions evoked by both glutamate (10−4moll-1) and L-quisqualic acid (10− 4moll− 1) were abolished by Immoll− 1 trimetaphan. Dose-response curves for ionophoresis of L-glutamate were shifted to the right by trimetaphan, with a reduction in peak glutamate potential amplitude. The depression of the ionophoretic glutamate potential was partly dependent upon previous stimulation history, and this action was eliminated by concanavalin A. Trimetaphan had no effect on transmitter release. Within certain limits, trimetaphan reduced the extracellular postsynaptic current (EPSC) amplitude and rise time in a concentration-dependent and voltage-dependent manner. At high concentrations (>5x 10− 4mol l− 1) its effectiveness was reduced with large hyperpolarizations. The EPSC decay was prolonged and usually biphasic in the presence of trimetaphan, although at some junctional sites a mixture of biphasic and apparently monophasic EPSC decays was seen. It is concluded that trimetaphan exerts more than one effect on locust muscle glutamate receptors. It is likely that it enhances desensitization and also blocks the receptor channel when in the open state.
