The effect of repetitive neuromuscular activity on the sensitivity of acetylcholine receptors.

If skeletal frog muscle is indirectly stimulated at 10 Hz first an increase and later a decrease of the amplitude of miniature end-plate currents (m.e.p.cs) is observed (Ruzzier and Scuka 1979). The underlying mechanism can be a presynaptic change of the quantal size or a postsynaptic change. To distinguish between these possibilities, the neurally evoked end-plate current (e.p.c.n), the ionophoretically evoked end-plate current (e.p.c.i) and the extracellularly recorded miniature end-plate potential (m.e.p.p.e) were studied. It was found that the time constant of decay of m.e.p.p.e did not change during the experiment. The amplitude of the e.p.c.i changed in the same way as the amplitude of the m.e.p.c., it first increased and then decreased. Similar changes of the amplitude of e.p.c.i were observed in the experiments with increased frequency of the nerve stimulation and in those with different increases of the quantal content. It is concluded that during prolonged repetitive stimulation the sensitivity of the end-plate receptors to the released transmitter is modified, probably as a consequence of the cooperative binding of acetylcholine to the receptors.