Untitled

Abstract

The effect of 5-hydroxytryptamine (serotonin) on neuromuscular transmission in frog skeletal muscle was studied using voltage clamp technique. Serotonin produced no effect on end-plate currents during low frequency electrical stimulation of the motor nerve, but increased the amplitude depression of multiquantal currents during high-frequency stimulation similar to motor commands fired by motoneurons. It was shown that the inhibitory effect of serotonin on neuromuscular transmission is determined by slow potential-dependent block of open ionic channels in the postsynaptic membrane accumulating during rhythmic activation of the synapse.

Trapping blockage of muscle nicotinic cholinoreceptors by mecamilamine

“…Hill's constant was practically the same as for neuronal cholinoreceptors ( n H = 1.1 [6]), which indicated that the channel was blocked by a single molecule of the blocking agent, whereas the concentration at which the blocking-agent effect was half the maximum ( I C 50 ) for muscle cholinoreceptors was considerably higher than that for neuronal receptors (0.34 µ M [6]). The latter suggests that mecamilamine has a smaller blocking effect on muscle cholinoreceptors.With respect to its EEC time-amplitude characteristics, mecamilamine is analogous to a desensitization promoter or a slow blocking agent of open channels, whose characteristic property is the enhancement of the inhibiting effect upon increasing the frequency of nerve stimulation [10][11][12]. However, our experiments with mecamilamine showed that the increase in the frequency of nerve stimulation to 10 Hz did not induce additional changes in current amplitudes, which indicates another action mechanism of this compound.…”

“…With respect to its EEC time-amplitude characteristics, mecamilamine is analogous to a desensitization promoter or a slow blocking agent of open channels, whose characteristic property is the enhancement of the inhibiting effect upon increasing the frequency of nerve stimulation [10][11][12]. However, our experiments with mecamilamine showed that the increase in the frequency of nerve stimulation to 10 Hz did not induce additional changes in current amplitudes, which indicates another action mechanism of this compound.…”

“…Experiments were carried out using an isolated neuromuscular preparation (sciatic nerve-sartorius muscle) of Rana ridibunda frogs using the standard technique of two-electrode potential fixation described earlier [10]. After infrequent nerve stimulations ( f = 0.05 Hz), mecamilamine at concentrations of 5-20 µ M induced dose-dependent decrease in the amplitude and the decay time constant of evoked endplate currents (EECs).…”

The Mechanisms Underlying Modulation of the Receptor-Channel Complex Functioning by Chlorhexidine

“…It has been previously suggested that chlorhexidine has a channel-blocking effect on a neuromuscular junction [1], although the type and mechanisms of this blockage remain unclear. Therefore, in this study, we analyzed the mechanism underlying the chlorhexidine effect on the receptor-channel complex of the muscle cholinoreceptor.Isolated neuromuscular preparations (sciatic nervetailor's muscle) were obtained from frogs by a previously described standard two-electrode voltage clamp procedure [2]. Under rare electric stimulation (0.05 Hz), chlorhexidine at concentrations of 2-15 µ M caused a concentration-dependent decrease in the amplitude and the time constant of the decline of evoked postsynaptic currents (EPCs).…”

“…Isolated neuromuscular preparations (sciatic nervetailor's muscle) were obtained from frogs by a previously described standard two-electrode voltage clamp procedure [2]. Under rare electric stimulation (0.05 Hz), chlorhexidine at concentrations of 2-15 µ M caused a concentration-dependent decrease in the amplitude and the time constant of the decline of evoked postsynaptic currents (EPCs).…”