Giniatullin_1997_J.Physiol_502_641

1. The desensitization induced by bath-applied carbachol or acetylcholine (ACh) and potentiated by proadifen (SKF 525A) was studied in the frog sartorius with intact synaptic acetylcholinesterase (AChE). 2. The reduction in the density and number of postsynaptic receptors produced by desensitization lowered the amplitude of the endplate currents (EPCs) and shortened the EPC decay when the quantal content (m) of the EPC was about 170 and when multiple release of quanta at single active zones was highly probably. The shortening of high-quantal-content EPCs persisted for at least 15 min after the wash-out of agonists, at a time when the amplitude had recovered fully. 3. The decay times of the low-quantal-content EPCs recorded from preparations pretreated with 5 mM Mg2+ (m approximately 70) and single-quantum miniature endplate currents (MEPCs) were not affected by carbachol, ACh or proadifen. 4. The desensitization of ACh receptors potentiated by proadifen, prevented completely the 6- to 8-fold prolongation of EPC which was induced by neostigmine inhibition of synaptic AChE. 5. It is assumed that high-quantal-content EPCs increase the incidence of multiple quanta release at single active zones and the probability of repetitive binding of ACh molecules which leads to EPC prolongation. The shortening which persists after complete recovery of the amplitude during wash-out of the exogenous agonist is probably due to 'trapping' of ACh molecules onto rapidly desensitized receptors and the reduced density of functional AChRs during the quantum action.