Contribution of glutamate receptors to spontaneous and stimulus-evoked discharge in afferent fibers innervating hair cells of the Xenopus lateral line organ

The relative contributions of NMDA (N-methyl-D-aspartate) and non-NMDA glut amate receptors to spontaneous and stimulus-evoked transmission at the hair cell/afferent fiber synapse were determined in the Xenopus laevis lateral line organ. The non-NMDA receptor antagonist, CNQX (6-cyano-7-nitroquinoxal ine-2,3-dione) reversibly reduced both spontaneous and stimulus-evoked disc harge rate with an EC50 of 0.5 mu M. NMDA receptor antagonism with the comb ination of chlorokynurenic acid (100 mu M) and elevated magnesium (1.1 mM), or elevated magnesium alone, blocked responses to NMDA without significant ly altering spontaneous or stimulus-evoked discharge rate or the responses to kainate. All non-NMDA receptor agonists tested increased discharge rate at low concentrations and. at higher concentrations, increased, then suppre ssed discharge rate. The EC(50)s were: domoic acid (2.4 mu M) < quisqualic acid (6 mu M) < kainic acid (18 mu M) < AMPA (82 mu M) << glutamate (1150 m u M). NMDA and ibotenic acid also produced an increase in discharge followe d by a suppression, but the suppressive phase of the response predominated and maximum increases in discharge rates were low compared to effects of th e non-NMDA agonists. The EC(50)s were: NMDA (148 mu M) < ibotenic acid (463 mu M). The EC50 for the suppression of afferent discharge that followed th e initial excitatory effect was similar to the EC50 for excitation. Perfusi on with active concentrations of kainate, AMPA. or NMDA did not alter the t hreshold for electrical stimulation of these nerve fibers. We conclude that most of the postsynaptic signal normally seen in afferent fibers is mediat ed by non-NMDA receptors. (C) 2000 Elsevier Science B.V. All rights reserve d.