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

Hear Res. 1991 Nov;56(1-2):143-7. doi: 10.1016/0378-5955(91)90163-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport, Active / drug effects
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cisplatin / toxicity*
  • Guinea Pigs
  • Hair Cells, Auditory / drug effects*
  • Hair Cells, Auditory / physiology
  • In Vitro Techniques
  • Ionomycin / pharmacology
  • Membrane Potentials

Substances

  • Calcium Channels
  • Ionomycin
  • Cisplatin
  • Calcium