The effect of repetitive stimulation on facilitation of transmitter release at the frog neuromuscular junction.

1. End-plate potentials (e.p.p.s) were recorded from frog neuromuscular junctions blocked with high Mg and/or low Ca to characterize the processes underlying increased transmitter release during repetitive stimulation.2. There was a progressive increase in the amplitude of successive e.p.p.s during repetitive stimulation. Increasing the frequency or duration of stimulation increased this facilitation of e.p.p. amplitudes. Facilitation is defined as the fractional increase in amplitude of a test e.p.p. over a control.3. By assuming that each impulse in a train contributes an identical increment of facilitation that sums linearly with the facilitation contributed by the previous impulses, estimates of the facilitation contributed by a single impulse, f(t), were made from the incremental increase in e.p.p. amplitudes during repetitive stimulation. The average value of f(t) contributed by the first impulse in the train during stimulation at 20/sec is given by f(t) = 0.8 e(-t/50) + 0.12 e (-t/300) + 0.025 e(-t/3000),where t is in msec. The first two terms in this equation were independent of the stimulation rate used to determine f(t) while the coefficient of the third term was a function of the stimulation rate, decreasing 2 to 3 times when the stimulation rate was decreased from 20/sec to 1/sec.4. This linear facilitation model predicted growth of e.p.p. amplitudes during the first several hundred msec of repetitive stimulation. Thereafter, e.p.p. amplitudes were typically facilitated more than predicted by the linear model.5. Several new methods are presented which can be used to obtain estimates of the magnitude and time course of facilitation contributed by specific impulses during repetitive stimulation.6. It is found that the value of short-term f(t) in the tested range of 25-300 msec progressively increases during repetitive stimulation while its time course of decay remains unchanged. After 9 sec of stimulation at 20/sec, the short-term f(t) increased to 1.4 times control.7. The increase in short-term f(t) was independent of whether it was determined from a step increase or decrease in total facilitation, excluding the possibility that the observed increase in short-term f(t) resulted from a change in the rate of decay of facilitation.8. It is suggested with supporting data from the following paper (Magleby, 1973) that each impulse contributes two types of facilitation that are responsible for the growth of e.p.p.s during repetitive stimulation: a short-term facilitation with linear summation properties described by the first two terms in the expression in paragraph 3 and a long-term cumulative facilitation approximated by the third term. The long-term facilitation is expressed as an increase in both the short-term facilitation and in the base level of transmitter release. The relative contribution of these two expressions of the long-term facilitation to the third term is a function of the stimulation rate and is given by the ratio of facilitation to the base level of transmitter release.