SUMMARY1. Desensitization to ionophoretically applied ACh has been studied at voltageclamped neuromuscular junctions of Rana pipien8.2. The time courses of both the onset of and recovery from desensitization displayed two components.3. The application of metabolic inhibitors to the preparation decreased the degree of recovery and also decreased both time constants of onset. The effect on onset was more pronounced on the slow component while no effect selective for either of the two components of recovery was seen.4. Intracellular injection of EGTA into the muscle cell increased both time constants of desensitization onset. The effect was much more pronounced on the slow component.5. Increasing the dose of ACh selectively decreased the fast time constant of desensitization onset. The effect was more selective in low-calcium than normal Ringer solution.6. These observations suggest that there are at least two independent mechanisms in the process of desensitization at the neuromuscular junction. These mechanisms differ in time course, degree of dependency on [Ca]i, and sensitivity to acetylcholine dose.

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