Post-tetanic potentiation of acetylcholine release at the frog neuromuscular junction develops after stimulation in Ca2+-free solutions.

Abstract

At many synapses, previous activity increases the amount of transmitter released by a single action potential. This potentiation oftransmitter release is usually attributed to the local accumulation of the calcium ions that cross the axolemma during an action potential. We found that potentiated transmitter release can be observed at frog neuromuscular junctions after periods of repetitive stimulation in Ca2+-free solutions, if Ca2+ is restored after the tetanus. Potentiation is greater and more prolonged, the lower the level ofextracellular KV. This component ofpotentiation may be due to Ca2+ that accumulates within the terminal in exchange for intracellular Na+.The passage of an action potential along the motor nerve ter-

Posttetanic potentiation at the crayfish neuromuscular junction is dependent on both intracellular calcium and sodium ion accumulation

“…Atwood et al (1975) showed at the crayfish NMJ that a lowered external sodium concentration reduced PTP, whereas conditions that led to increased sodium loading through inhibition of Na/K exchange prolonged PTP. Other investigators confirmed that elevating [Na+], by similar methods augmented PTP, both at the frog (Rahamimoff et al, 1978;Lev-Tov and Rahamimoff, 1980;Misler and Hurlbut, 1983;Misler et al, 1987) and rat NMJ (Nussinovitch and Rahamimoff, 1988). Sodium injected directly into presynaptic terminals ofthe crayfish axon (Wojtowicz and Atwood, 1985) and the squid giant synapse (Charlton and Atwood, 1977) also enhanced transmitter release.…”

“…Nussinovitch and Rahamimoff (1988) in the mammal; Lev-Tov and Rahamimoff (1980) Misler and Hurlbut (1983), and Misler et al (1987) in the frog; and Swenarchuk and Atwood (1975) in the crayfish showed that stimulation in a calcium-free medium produced some PTP after normal calcium was restored. Stimulation at high frequencies, like that needed to induce PTP, in a nominally calcium-free Ringer's can lead to calcium entry and even transmitter release, as shown recently at the crayfish NMJ (Mulkey and Zucker,199 1 a).…”

“…Reversal of NalCa exchange under physiological conditions occurs only when internal sodium is high and external sodium is low It has been suggested PTP may be due to a reversed Na/Ca exchange that takes place during and following tetanic stimulation (Misler and Hurlbut, 1983;Misler et al, 1987). The equation for the reversal potential for a 3: 1 Na/Ca exchanger is 3E,, -2.Q = Gwca.…”

“…At the crayfish NMJ, ouabain prolonged PTP and greatly enhanced EJP amplitude (Wojtowicz and Atwood, 1985). Prolongation of PTP was also obtained at the frog (Rahamimoff et al, 1978;Lev-Tov and Rahamimoff, 1980;Misler and Hurlbut, 1983;Misler et al, 1987) and rat NMJ (Nussinovitch and Rahamimoff, 1988). Ouabain experiments performed in zero-calcium solutions to determine mechanism of sodium elevation were done at the mammalian and frog NMJ.…”

Implication of frequenin in the facilitation of transmitter release in Drosophila.

“…Possible involvement of impulse-dependent Na+ accumulation inside nerve terminals in the Frq-dependent enhancement of facilitation of transmitter release is strongly suggested by the tetrodotoxin and low-Na+ experiments. It has long been recognized that increases in internal Na+ promote enhanced transmitter release by nerve terminals (Birks & Cohen, 1968;Baker & Crawford, 1975;Atwood et al 1983;Misler & Hurlbut, 1983;Nussinovitch & Rahamimoff, 1988). At least two possible mechanisms may be involved in the sodium effect on transmitter release: (i) reduction of the Ca2+ extrusion by the Na'-Ca2" exchanger leading to calcium retention; and (ii) release of calcium from internal stores.…”