Regenerated hair cells become functional during continuous administration of kanamycin

The compound action potential (CAP) was used to assess the functional status of regenerated hair cells in the chick cochlea during prolonged administration of kanamycin (KM). Immediately after 10 days of KM treatment, the CAP thresholds were elevated by 6-54 dB above those from age-matched control animals. The frequencies with the greatest threshold shifts (> 1 kHz) corresponded to the hair cell lesion in the basal 40% of the basilar papilla. After 20 days of KM, the CAP thresholds at 3 and 4 kHz were significantly lower than those after 10 days of KM treatment, but virtually the same as those after 10 days of KM plus 10 days of recovery. Similarly, the CAP amplitudes at frequencies higher than 1.5 kHz were significantly greater in animals that received KM for 20 days than in animals that received KM for 10 days. The threshold as well as amplitude improvement between 10 days and 20 days of KM treatment was associated with the morphological maturation of the regenerated hair cells in the basal 25% of the cochlea. In addition, the rapid functional recovery seen at high frequencies coincided with the base-to-apex gradient of morphological recovery in the basilar papilla. These results suggest that the process of hair cell maturation is not suppressed by the presence of aminoglycosides in the extracellular environment.