Prolonged nerve stimulation causes changes in transmitter release at the frog neuromuscular junction.

1. Synaptic transmission in the two cutaneus pectoris muscles of frog was compared after prolonged unilateral nerve stem stimulation in vivo via surface electrodes. 2. In Mg2+-blocked preparations at 2 Hz stimulation the mean number of quanta released per impulse (m) was significantly lower in the stimulated muscles. On average, m was reduced to 53% (range 31-74%) of the values in control muscles. 3. Similarly, in curare-blocked preparations end-plate potential (EPP) amplitudes in the stimulated muscles were reduced to 30-92% (average 63%) of the control values, while no differences in muscle fibre diameter and resting potential were detectable. 4. In most muscles plateau values after tetanic stimulation at 40 Hz for 2 s were also smaller in the stimulated muscles. Compared to the first EPP in the train, however, plateau values were less depressed in stimulated than in unstimulated muscles. Also facilitation, i.e. the amplitude ratio of the largest versus the first EPP was more pronounced in stimulated muscles. 5. No effects of stimulation were noticed in four winter frogs, in which transmitter release is depressed due to seasonal factors. 6. It is concluded that prolonged nerve stimulation can cause under certain conditions profound depression of transmitter release with changes in facilitation and depression.