THE ORIGINS AND MECHANISM OF GLUTAMATE RELEASE IN COCHLEA

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We applied microdialysis technique to investigate the perilymphatic glutamate. The glutamate concentration was analyzed continuously by enzyme-linked fluorometric assay combined with microdialysis. (1) The time course of changes in perilymphatic glutamate were observed during the application of kanamycin and ethacrynic acid, which are known to damage the hair cells in the inner ear. In guinea pigs receiving a loading dose of 800 mg/kg of kanamycin subcutaneously, followed three hours later by an intravenous injection of 40 mg/kg of ethacrynic acid, a marked glutamate release was clearly found about 2 hours after the injection of ethacrynic acid. The present findings provide additional evidence that glutamate acts as an aggravating factor in aminoglycoside-induced ototoxicity. (2) A glutamate release observed in the same model shown above was completely inhibited in the absence of extracellular Ca^<2+>. This observation shows extracellular Ca^<2+> play an important role in drug-induced ototoxicity. (3) The time course of changes in perilymphatic glutamate were studied in the normal or deaf guinea pig cochlea during cardiac arrest. In normal animal slightly efflux of glutamate was observed within 10 min after cardiac arrest. This was completely inhibited in the absence of extracellular Ca^<2+>. Marked glutamate efflux only occurred 10 min after cardiac arrest in Ca^<2+>-independent manner. In deaf animals there was no glutamate release in 1 hr after cardiac arrest. The present findings suggest that during the cardiac arrest, most of the released glutamate is of non-vesicular origin, probably from both inner and outer hair cells.