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.
Saito
T
T
Laboratoire d'Audiologie Expérimentale, INSERM unité 229, Université de Bordeaux II, Hôpital Pellegrin, France.
Moataz
R
R
Dulon
D
D
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D008564:Membrane Potentials
D015220:Calcium Channels; D015759:Ionomycin; D002945:Cisplatin; D002118:Calcium