The effect of non-quantal acetylcholine release on quantal miniature currents at mouse diaphragm

1. The amplitude and exponential decay time constant of miniature endplate currents (MEPCs) were measured in mouse diaphragms treated with anti-cholinesterase under conditions known to modulate non-quantal acetylcholine (ACh) release. 2. Anti-cholinesterase prolonged MEPC decay and the extent of this initial prolongation was not influenced by non-quantal release. When non-quantal release was present, the decays of MEPCs became increasingly faster over several hours. This increased decay did not occur in the absence of non-quantal release. 3. Potentiation of the non-quantal release by zero Mg2+ and 1 x 10(-5) M choline, on the other hand, led to acceleration of MEPC shortening. 4. Increase of temperature from 15 to 26 degrees C and the presence of the desensitization-promoting drug proadifen (5 x 10(-6) M) accelerated the rate of MEPC shortening. 5. These observations are consistent with increased receptor desensitization due to non-quantal release. Repetitive binding of ACh to postsynaptic receptors which prolongs the time course of MEPC in anti-cholinesterase-treated endplates leads to progressive desensitization in the presence of non-quantal release and to the subsequent shortening of the quantal responses.