Kanamycin and bumetanide ototoxicity: anatomical, physiological and behavioral correlates

Severe hair-cell degeneration and cochlear dysfunction was observed in chinchillas examined at 60 days (or longer) after administration of a single injection of 150 mg/kg kanamycin, followed 2 h later by a single injection of 20 mg/kg bumetanide. Outer hair cells in the cochlear base were most severely affected. While inner and outer hair-cell loss was common, some animals showed large regions along the basilar membrane where almost all inner hair cells were present and almost all outer hair cells were absent. Wherever areas of complete degeneration of the organ of Corti occurred, a small, diffuse population of nerve fibers within the spiral lamina was always present. Single-unit tuning curves correlated best with anatomical observations, compared with the other functional measures of auditory sensitivity that were obtained (behavioral audiogram and compound action potential thresholds). Results indicated that behavioral detection of auditory stimuli is relatively independent of innervation density as long as a few inner hair cells are present. Thus, the cross-fiber threshold envelope of the single-unit tuning curves appeared very similar to the behavioral audiogram.