Dependence of acetylcholine desensitization on the membrane potential of frog muscle fibre and on the ionic changes in the medium.

1. The rate of desensitization of the post-synaptic membrane to prolonged action of acetylcholine was investigated during (a) potassium depolarization of the frog muscle fibre, (b) artificial changes of the membrane potential and (c) in the presence of some multivalent cations and of caffeine.2. Depolarization of the muscle fibre by 15 mM-K(+) led to a slowing down in the development of desensitization by 80%. This effect on desensitization produced by membrane potential changes could account for the previously described effect of increased K(+) concentration.3. Electrotonically produced depolarization of the muscle fibre membrane resulted in a decrease, hyperpolarization in an increase of the rate of desensitization.4. Several multivalent cations can be, according to their ability to increase rate of desensitization, arranged in the following series: [Formula: see text]5. Caffeine in a concentration of 1.5 mM does not affect the rate of desensitization.6. A hypothesis is presented suggesting that desensitization is not only restricted to the receptor level but that it also occurs, at least partly, at the terminal stages of the activation system.