Secretion of acetylcholine in response to graded depolarization of motor nerve terminals.

1. Depolarizing current pulses were used to elicit transmitter secretion from motor nerve terminals in mouse phrenic nerve-diaphragm preparations exposed to solutions containing tetrodotoxin and 4-aminopyridine. 2. The amplitude of end-plate potentials (e.p.p.s.) elicited by depolarizing pulses was depressed for several milliseconds following a hyperpolarizing pulse, and potentiated following a subthreshold depolarizing pulse. Recovery followed an exponential time-course with time constant of 1.5 to 2.5 ms. 3. The time constant of nerve terminals, calculated from strength-duration curves obtained with depolarizing current pulses that elicited transmitter secretion, ranged from 1.5 to 2.56 ms. 4. It was concluded that the nerve terminal time constant would explain the effects of conditioning polarizations if there were a presynaptic "threshold potential" for end-plate potentials. The decrease in latency of e.p.p.s. as stimulus strength was increased could be explained in the same way. 5. The amplitude of e.p.p.s. increased as depolarizing pulses were lengthened from 2 to 10 ms. When a brief depolarizing pulse was superimposed on a longer subthreshold pulse, e.p.p. amplitude could not be related to the maximum depolarization of the presynaptic terminal. Transmitter secretion appeared to depend on both the level and duration of the depolarization.