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.
Subject(s)
Muscle, Skeletal/drug effects , Serotonin/pharmacology , Acetylcholine/metabolism , Acetylcholinesterase/pharmacology , Animals , Electrophysiology , Ions , Membrane Potentials , Muscle, Skeletal/metabolism , Neostigmine/pharmacology , Neurons/metabolism , Ranidae , Sciatic Nerve/metabolism , Serotonin/metabolism , Time FactorsABSTRACT
Experiments on the frog sartorius muscle were used to study the effects of the L-type calcium channel blocker verapamil on endplate currents. Verapamil had no effect on the amplitudes of miniature and multiple-quantum endplate currents, the synchronicity of transmitter secretion, or repeat activity in nerve endings. Verapamil had no effect on the decay of miniature currents, but accelerated that of multiple-quantum currents. This effect was sharply increased after inhibition of cholinesterase activity. In conditions of inhibited cholinesterase activity, verapamil depressed currents during rhythmic stimulation. This depression was more marked in synapses with high quantal compositions and in conditions of membrane depolarization. Thus, the sensitivity of neuromuscular junction calcium channels to verapamil was unrelated to the release of transmitter from the motor nerve ending either at physiological levels of secretion or when secretion was potentiated by potassium channel blockers. At the postsynaptic level, the effect of verapamil was insignificant in relation to cholinoreceptors in the resting and active states, though verapamil could cooperatively enhance the transition of postsynaptic receptors into the desensitized state in conditions of prolonged transmitter action.
Subject(s)
Calcium Channel Blockers/pharmacology , Neuromuscular Junction/drug effects , Verapamil/pharmacology , Acetylcholinesterase/metabolism , Animals , In Vitro Techniques , Muscle Contraction/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/innervation , Neuromuscular Junction/enzymology , Rana ridibunda , Sciatic Nerve/drug effectsABSTRACT
Verapamil did not change the amplitude of the miniature and multiquantal end-plate currents, synchronicity of the transmitter release and repetitive firing at the motor nerve endings. Verapamil shortened the decay of multiquantal currents, the effect being enhanced after acetylcholinesterase inhibition. In muscles with inhibited acetylcholinesterase, verapamil promoted the depression of successive end-late currents in rhythmic nerve stimulation. The data suggest that in skeletal muscles verapamil-sensitive calcium channels do not take part in physiological transmitter release or in chemical potentiation of the secretion after treatment with potassium channels blocking agents.
