Neurotransmitter release from hair cells and its blockade by glutamate-receptor antagonists

To assess the mechanism by which glutamate-receptor antagonists block afferent discharge at the hair cell synapse, we examined the effects of these and other agents on sound-evoked excitatory post-synaptic potentials (EPSPs) and on spontaneous miniature post-synaptic potentials (MEPSPs) in auditory-nerve fibers of the goldfish (Carassius auratus) saccule. A quantal analysis of synaptic transmission under conditions in which the probability of transmitter release was reduced by cobalt, an agent that can block transmitter release, supports Furukawa's (Jpn. J. Physiol. 36, 1059-1077, 1986) conclusion that transmitter release at this synapse is quantal. Cobalt reduced the rate of occurrence of spontaneous MEPSPS without reducing their amplitude. The glutamate-receptor antagonists, gamma-D-glutamyl glycine (DGG) and 5-aminophosphonovaleric acid (APV) both reduced the amplitude of sound-evoked EPSPs much more than that of the spontaneous MEPSPs. The glutamate-receptor agonists, L-glutamate, kainate, and quisqualate, produced a depolarization of the afferent nerve fiber, a decrease in the amplitude of the EPSP and an increased tendency for an EPSP to generate an action potential.