Ionic mechanism of post‐tetanic potentiation at the neuromuscular junction of the frog

Abstract

SUMMARY1. 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.

The physiology, pharmacology, and trophic effectiveness of synapses formed by autonomic preganglionic nerves on frog skeletal muscle.

“…junctions is not clear. It is generally accepted that the potentiation of release at normal frog neuromuscular junctions is due to a build-up of intraterminal Ca2 , which leads primarily to an increase in the probability ofrelease rather than to an increase in available transmitter A. D. GRINNELL AND M. B. RHEUBEN stores (Rosenthal, 1969;Weinreich, 1971 Post-synaptic physiology does reveal differences attributable to the abnormal nerve supply. As Landmesser (1972) observed for vagal-reinnervated frog sartorius fibres, there is no histochemical or physiological evidence for cholinesterase at the new junctions.…”

The effect of calcium ions on the binomial statistic parameters which control acetylcholine release at synapses in striated muscle.

“…Asp increases linearly with the increase in [Ca], which accompanies the action potential, and post-tetanic potentia-444 EFFECT OF Ca ON ACh RELEASE tion is due to a slow increase ofp during continual high-frequency stimulation, there should be a small increase in the basal level of [Ca], during continual high-frequency stimulation. This is the case (Baker et al 1971;Llinas, Blinks & Nicholson, 1972), and explains why post-tetanic potentiation is solely dependent on Ca (Weinreich, 1971), and why during potentiation there is an increase in the basal level of transmitter release (Magleby, 1973a).…”

The dependence of evoked transmitter release on external calcium ions at very low mean quantal contents

“…Perhaps more convincingly, the model predicts that changes in [Ca]R at fixed ACa should change m only when this is very low. Yet experimental manipulations thought to raise [Ca]R such as during facilitation (Katz & Miledi, 1968;Weinreich, 1971) and exposure of end-plates to the calcium ionophore nystatin (Crawford & Fettiplace, 1971) produce changes in m at quantal contents high enough to be in the fourth power part of the calcium dependence curve. Even when m has been increased by nystatin treatment the calcium dependence m retains its fourth power dependence on [Ca]o (Crawford & Fettiplace, 1971).…”