The effect of procaine on the action of acetylcholine at the neuromuscular junction.

1. The effect of procaine on acetylcholine-induced membrane fluctuations (ACh noise) was studied by intracellular and focal external recording from end-plates of frog sartorius muscle. 2. With intracellular recording, ACh noise (the ratio of variance to mean depolarization) was substantially reduced by procaine, suggesting a greatly decreased amplitude of the elementary potential change. 3. Spectral analysis of the ACh noise indicated a dual average time course of the underlying "shot effects", similar to the complex shape (brief spike followed by a long tail of low intensity) of the end-plate current in pro-aine-treated muscle. 4. The post-synaptic blocking action of procaine can be largely explained by the drastic shortening of the initial high-intensity phase of the end-plate conductance change. 5. The average time course of the ACh shot effects is discussed in terms of alternative hypotheses, one attributing the complex shape to each elementary event, the other involving sequential reaction steps which produce two unequal populations of ion gates of different "life-times".