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

Abstract

The relative contributions of NMDA (N-methyl-D-aspartate) and non-NMDA glutamate 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-nitroquinoxaline-2,3-dione), reversibly reduced both spontaneous and stimulus-evoked discharge rate with an EC(50) of 0.5 microM. NMDA receptor antagonism with the combination of chlorokynurenic acid (100 microM) and elevated magnesium (1.1 mM), or elevated magnesium alone, blocked responses to NMDA without significantly 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 suppressed discharge rate. The EC(50)s were: domoic acid (2.4 mcM)<quisqualic acid (6 mcM)<kainic acid (18 mcM)<AMPA (82 mcM)<<glutamate (1150 mcM). NMDA and ibotenic acid also produced an increase in discharge followed by a suppression, but the suppressive phase of the response predominated and maximum increases in discharge rates were low compared to effects of the non-NMDA agonists. The EC(50)s were: NMDA (148 mcM)<ibotenic acid (463 mcM). The EC(50) for the suppression of afferent discharge that followed the initial excitatory effect was similar to the EC(50) for excitation. Perfusion with active concentrations of kainate, AMPA, or NMDA did not alter the threshold for electrical stimulation of these nerve fibers. We conclude that most of the postsynaptic signal normally seen in afferent fibers is mediated by non-NMDA receptors.