ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONIC-ACID ELECTROPHYSIOLOGICAL AND NEUROTOXIC EFFECTS IN THE GUINEA-PIG COCHLEA

We have recorded cochlear potentials after perilymphatic perfusion of cumulative doses of the excitatory amino acid alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) which selectively recognizes the non-N-methyl-D-aspartate ionotropic receptor formerly known as the quisqualate receptor. Our results show that AMPA (1-80-mu-M) caused a significant suppression of the amplitude of the compound action potential evoked by acoustic stimulation. A total elimination of this potential at the 100-mu-M concentration was observed in all animals. In no case was the cochlear microphonic potential, a hair cell receptor potential, affected by AMPA. Histological examinations were performed either at the end of the physiological studies or on cochleas perfused for 10 min with a single dose of AMPA (50 or 100-mu-M). In both experimental conditions, a selective dendritic swelling or radial aferent nerve endings under the sensory inner hair cells was observed. No damage was found in both types of hair cells supporting cells, lateral and medial efferent fibers and spiral afferent nerve ending on the outer hair cells. The occurrence of the radial dendrite swelling was prevented when 6,7-dinitroquinoxaline-2,3-dione (500-mu-M) was perfused in the cochlea 10 min prior, then concomitantly with AMPA. The present study strongly suggests that non-N-methyl-D-aspartate receptors, possibly of the AMPA subtype, are involved in the synaptic transmission between the inner hair cells and the primary auditory neurons. They provide further support for the hypothesis that L-glutamate, or another excitatory amino acid, acts as an inner hair cell neurotransmitter.