Mechanisms underlying the vecuronium-induced tetanic fade in the isolated rat muscle.

The cellular mechanisms underlying the effects of vecuronium on the tetanic contraction were studied in vitro with a combination of myographic and electrophysiologic techniques. We used the isolated sciatic nerve extensor digitorum longus muscle preparation of the rat. Indirect twitches were evoked at 0.1 Hz pulses and tetani at 50 Hz pulses. Trains of end-plate potentials were generated at 50 Hz. The electrophysiological variables used in the analysis of the end-plate potentials were: amplitude, tetanic run-down, quantal size and quantal content. The myographic study demonstrated that vecuronium at 0.4 microM caused tetanic fade, but left the twitch unaffected. Regarding electrophysiology, vecuronium (0.4 microM) decreased the amplitude of end-plate potentials and increased their tetanic run-down. These changes were due to significant reductions in both the quantal content of the end-plate potentials and the quantal size. It is concluded that vecuronium has both pre- and postsynaptic effects at the neuromuscular junction, and that it induces fade of the tetanic contraction via a summation of these effects.