THE EFFECT OF NONQUANTAL ACETYLCHOLINE-RELEASE ON QUANTAL MINIATURE CURRENTS AT MOUSE DIAPHRAGM

1. The amplitude and exponential decay time constant of miniature endp late currents (MEPCs) were measured in mouse diaphragms treated with a nti-cholinesterase under conditions known to modulate non-quantal acet ylcholine (ACh) release.2. Anti-cholinesterase prolonged MEPC decay an d the extent of this initial prolongation was not influenced by non-qu antal release. When non-quantal release was present, the decays of MEP Cs 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 t he other hand, led to acceleration of MEPC shortening. 4. Increase of temperature from 15 to 26-degrees-C and the presence of the desensitiz ation-promoting drug proadifen (5 x 10(-6) m) accelerated the rate of MEPC shortening. 5. These observations are consistent with increased r eceptor desensitization due to non-quantal release. Repetitive binding of ACh to postsynaptic receptors which prolongs the time course of ME PC in anti-cholinesterase-treated endplates leads to progressive desen sitization in the presence of non-quantal release and to the subsequen t shortening of the quantal responses.