DESENSITIZATION OF AMPA RECEPTORS UPON MULTIQUANTAL NEUROTRANSMITTER RELEASE

We have investigated the role of AMPA receptor desensitization during transmission at a calyceal synapse. Cyclothiazide blocked the rapid de sensitization of AMPA receptors and markedly prolonged the decay time of the evoked excitatory postsynaptic current (PSC). This effect was g reater than what would be expected from a simple prolongation of chann el open time. Additionally, the drug reduced the depression of PSCs ev oked at brief intervals. The effects of cyclothiazide on the PSC were reduced when the level of transmitter release was lowered. These data indicate that AMPA receptors are de sensitized by neurotransmitter and that this desensitization depends on the number of quanta in the syna ptic cleft. We propose that release of transmitter from many closely s paced sites prolongs the time of receptor-transmitter contact and ther eby promotes desensitization. Desensitization may therefore contribute to synaptic depression and prevent the interaction of transmitter qua nta within the synaptic cleft.