Analysis of perilymphatic glutamate by in vivo microdialysis study

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We applied microdialysis technique to investigate the perilymphatic glutamate.(1) The time course of changes in perilymphatic glutamate release and their Ca^<2+>-dependency were studied in the guinea pig cochlea during high K^+-evoked depolarization. Two peaks of glutamate increase were found in response to perfusion for 10 min. In the absence of Ca^<2+> the first peak was diminished, whereas the inhibition of the second peak was minimal.(2) The dynamic changes in perilymphatic glutamate and cochlear blood flow were studied in the guinea pig cochlea during occulusion of anterior inferior cerbellum artery (AICA). The result of this study indicate that the glutamate regulating system in the cochlea is dependnt on cochlear blood flow.(3) 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 provideadditional evidence that glutamate acts as an aggravating factor in aminoglycoside-inducedototoxicity.Kanamycin (KM) -induced changes in the gene expression for glutamate-aspartatetransporter (GLAST) in the rat cochlea were analyzed by Northern blotting. With theadministration of KM (600 mg/kg/day) once daily for 20 days, the expression of GLAST mRNAgradually increased and reached a peak on day 20. Although the expression of GLAST mRNA remained at a high level at 12 days after the completion of the KM treatment, it then fellto the normal level within 2 months. The present findings suggest that during the KMadministration, high concentrations of extracellular glutamate released by collapsing haircells induced GLAST mRNA expression.