A comparison of the time course of excitation and inhibition by iontophoretic decamethonium in frog endplate.

1 The depolarization of frog endplate by a brief iontophoretic application of decamethonium was slower in time course than the inhibition of a long carbachol response produced by the same decamethonium pulse, or than the excitation produced by a brief equipotent carbachol pulse. 2 The delay between the peak inhibition and peak excitation produced by decamethonium, about 50 ms, is too great to be explained by slow receptor activation kinetics, since Katz & Miledi (1973) have shown that the lifetime of decamethonium-activated receptors is only 0.25 milliseconds. 3 If doses of carbachol and decamethonium are adjusted to give response amplitudes in the ratio corresponding to the ratio of their presumed maximum responses, then there is little difference in the time courses of the responses. 4 This observation, together with the finding that increasing the dose applied slows the decamethonium response much more than the carbachol response, suggests that a decamethonium response contains contributions from a much wider area of receptive membrane than does a carbachol response of equal amplitude. 5 Simulation shows that these geometrical effects are sufficient to account for the rapidity of inhibition compared to excitation without postulating slow receptor kinetics. 6 It is pointed out that similar effects may account for certain results obtained in iontophoretic studies of desensitization.