Ionic mechanism of post-tetanic potentiation at the neuromuscular junction of the frog.

1. Transmitter release at the frog neuromuscular junction was studied after sodium influx in nerve and muscle was abolished by tetrodotoxin (TTX).2. In the presence of TTX, transmitter release evoked by electrotonic depolarization of the nerve terminal was potentiated following presynaptic stimulation by a train of depolarizing pulses.3. Post-tetanic potentiation (PTP) in the presence of TTX appeared no different from that observed in control (TTX-free) muscles. The magnitude as well as the time course of PTP was dependent on the number of tetanic stimuli and on temperature of the medium when sodium influx was inhibited by TTX.4. When external sodium was replaced by an isotonic calcium chloride solution PTP was still present. Ionophoretic application of calcium during tetanic nerve stimulation and increase in the intensity of the depolarizing pulse of the train, which presumably enhances calcium movements into nerve endings, caused a large increase in the duration of PTP.5. It is concluded that PTP does not require sodium but depends on movement of calcium from the external medium into the nerve terminal.