Calpain activity in the amikacin-damaged rat cochlea

The principal aim of this study was to investigate the involvement of calpain in the degeneration of hair cells and ganglion neurons in the amikacin-poisoned rat cochlea. An antibody designed against fodrin-breakdown products (FBDP), which result exclusively from cleavage by calpain, was used. In addition, the involvement of both caspases and protein kinase C (PKC) was studied using, respectively, Antibodies against activated Caspase 3 and PKCgamma. The results demonstrate the accumulation of FBDP in the degenerating hair cells, in some supporting cells such as Deiters cells, and, later, in the affected ganglion neurons that had been deprived of their sensory targets. Activated Caspase 3 was evidenced in a few dying hair cells and ganglion neurons. PKCgamma was highly expressed in all ganglion neurons, sometimes after the loss of hair cells. We conclude that calpain plays a role in the degradation of both the sensory cells and neurons after amikacin ototoxicity. In the poisoned hair cells, calpain and Caspase 3 may have synergistic effects in the process of Apoptosis. In the ganglion neurons deprived of their sensory elements, calpain may have a prominent role in cell degradation. By contrast, in these ganglion neurons PKCgamma may be implicated in a survival process. Finally, we suggest that calpain is involved in the remodeling of Deiters cells during the scarring process that follows hair cell loss.