Pharmacology of afferent synaptic transmission in the goldfish inner ear.

摘要

The hair cells of the inner ear release a neurotransmitter which produces excitatory post-synaptic potentials (EPSPs) in the afferent auditory neurons. The afferent neurotransmitter is unknown, but has been proposed to be an excitatory acidic amino acid or a related substance. We investigated the site and mechanism of action of excitatory amino acid agonists and antagonists at the hair cell-afferent neuron synapse. To accomplish this, the action of these drugs was studied at the level of quantal events in synaptic transmission in the goldfish sacculus in situ.; First, the hypothesis that transmission at the hair cell-afferent synapse is quantal was examined. Amplitudes of sound evoked EPSPs were reduced until quantal fluctuations were observable. Amplitudes of many evoked EPSPs were measured, as were amplitudes of spontaneous miniature synaptic potentials (MEPSPs) recorded in silence. The experimentally determined EPSP amplitude distributions were compared with theoretical amplitude distributions predicted from the quantal hypothesis, modeling quantal release as a Poisson process and taking the MEPSP amplitude to be the size of the quantal event. When transmitter release was reduced by using a low acoustic stimulus, there was poor agreement of the observed distributions with the theoretical ones. However, when transmitter release was blocked with cobalt ions in the presence of a loud acoustical stimulus, the measured distributions agreed well with the theoretical quantized ones.; Two excitatory amino acid antagonists, {dollar}gamma{dollar}-d-glutamylglycine (DGG), 1.0 mM, and 5-amino-2-phosphonovaleric acid (APV), 1.0 mM, reversibly decreased the amplitude of sound-evoked EPSPs. Both drugs reduced the amplitudes of MEPSPs recorded in silence, but suppressed sound-evoked EPSP amplitudes to a much greater extent than MEPSP amplitudes. The rate of release of MEPSPs was not greatly affected. The results were interpreted to indicate that the antagonists act by at least two mechanisms: a presynaptic mechanism in which the antagonists reduce the synchronized release of transmitter quanta from hair cells and an additional mechanism in which the drugs act to decrease the size of the quantal event itself. This latter effect could occur postsynaptically or presynaptically. The effects of several excitatory amino acid agonists on EPSPs and MEPSPs were also studied, and were found to be consistent with a postsynaptic action on afferent terminals. The results support the view that the receptors for the hair cell-afferent neuron transmitter are pharmacologically related to the excitatory amino acid receptors of the central nervous system.