Cisplatin blocks depolarization-induced calcium entry in isolated cochlear outer hair cells

The effects of the ototoxic molecule cisplatin (cis-DDP) were tested on the physiology of isolated cochlear outer hair cells. Cis-DDP, even at a high concentration of 1 mM, did not affect the viability of the OHCs maintained in short-term culture in vitro (6 h following cell dissociation was the longest time tested). Also, the presence of cis-CDP (1 mM) did not inhibit the contractile responses of the OHCs stimulated by the external application of the calcium ionophore, ionomycin. However, cis-DDP was able to block calcium entry evoked by [K+]-depolarization and a dose-inhibition curve indicated an IC50 of 45 +/- 30 microM. These results suggest that one of the acute actions of cis-DDP on OHCs physiology might be situated at the level of the plasma membrane where it acts as a Ca(2+)-channel blocker.