Control of quantal transmitter release at frog's motor nerve terminals. I. Dependence on amplitude and duration of depolarization.

Motor terminals on the cutaneous pectoris muscle of the frog were depolarized by current pulses through the recording macro-patch-clamp electrode and the resulting quantal release was measured (excitation blocked with TTX). Above a threshold release increased very steeply with depolarization until saturation was approached. The dependence of release on duration of depolarization was even steeper: doubling pulse duration often produced more than 100-fold release ('early facilitation'). Distributions of delays of quantal release after the depolarization pulse were determined for wide ranges of depolarizations and pulse durations. The shape of these distributions was little affected by large changes in average release; increasing the temperature from 0 degrees C to 10 degrees C about halved the time scale of the distributions. Lengthening the depolarization from 0.5 to 6 ms produced a 'latency shift': the distributions of delays were shifted by almost the increase in pulse duration. At 5-6 ms pulse duration a few releases occurred during the final millisecond of the pulse. It is suggested that the time course of the phasic release is not controlled by the time course of changes in intracellular calcium concentration, but by an activator which is produced about proportional to supra-threshold pulse amplitude and duration, and that this activator effects release with a cooperativity of 6-7. An additional depolarization produced repressor is responsible for the minimum delay.