Effect of prostigmine on the time course of the end-plate potential in the rat diaphragm.

1. End-plate potentials (e.p.p.s) were evoked by applying brief depolarizing pulses to motor nerve endings in a phrenic nerve-diaphragm preparation paralysed by tetrodotoxin (TTX). Without prostigmine, the time to decay from the summit of the e.p.p. to half amplitude (the half-decay time) was roughly constant (2-4 msec) when the amplitude was increased by increasing stimulus intensity or duration.2. In the presence of prostigmine (5 x 10(-7)-2 x 10(-5) g/ml.), the falling phase of the e.p.p. was different in time course depending on the amplitude. The half-decay time had, very roughly, an exponential dependence on amplitude. The relationship was not affected by increasing the TTX or the prostigmine concentration, but D-tubocurarine (10(-6) g/ml.) made the relationship less steep.3. Hyperpolarizing current pulses, applied after the depolarizing current pulse which produced the e.p.p., had no effect on the time course of the e.p.p. No facilitating effect of repetitive stimulation was observed without prostigmine up to a frequency of 40 c/s, but there was a strong effect of repetitive stimulation in increasing the amplitude and duration of the e.p.p. in the presence of prostigmine. During stimulation, the endplate was continuously depolarized by 10-20 mV, and its recovery was very slow, the half-decay time being about 3 sec.4. The half-decay time of the acetylcholine potentials produced by iontophoretically applied acetylcholine was almost independent of the amplitude, with or without prostigmine, although it increased the amplitude of the potential and prolonged the falling phase.5. Possible mechanisms for the alteration of the falling phase of the e.p.p. were discussed. It is speculated that, in the presence of prostigmine, a process which is involved in a conductance increase of the post-synaptic membrane, after acetylcholine has combined with the receptor molecules, is the main factor determining the falling phase of the e.p.p.