AMPA-preferring glutamate receptors in cochlear physiology of adult guinea-pig

1. The present study was designed to determine which glutamate (Glu) recept ors are involved in excitatory neurotransmission at the first auditory syna pse between the inner hair cells and the spiral ganglion neurons. 2. The Glu receptors present at the membrane level were investigated on iso lated spiral ganglion neuron somata from guinea-pigs by whole-cell voltage- clamp measurements. Glu and AMPA induced a fast onset inward current that w as rapidly desensitized, while kainate induced only a non-desensitizing, st eady-state current. NMDA induced no detectable current. 3. To further discriminate between the AMPA and kainate receptors present, we used the receptor-specific desensitization blockers, cyclothiazide and c oncanavalin A. While no effect was observed with concanavalin A, cyclothiaz ide greatly enhanced the Glu-, AMPA- and kainate-induced steady-state curre nts and potentiated Glu-induced membrane depolarization. 4. To extrapolate the results obtained from the somata to the events occurr ing in situ at the dendrites, the effects of these drugs were evaluated in vivo. Cyclothiazide reversibly increased spontaneous activity of single aud itory nerve fibres, while concanavalin A had no effect, suggesting that the functional Glu receptors on the somata may be the same as those at the den drites. 5. The combination of a moderate-level sound together with cyclothiazide in creased and subsequently abolished the spontaneous and the sound-evoked act ivity of the auditory nerve fibres. Histological examination revealed destr uction of the dendrites, suggesting that cyclothiazide potentiates sound-in duced Glu excitotoxicity via AMPA receptors. 6. Our results reveal that fast synaptic transmission in the cochlea is mai nly mediated by desensitizing AMPA receptors.