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Cisplatin blocks depolarization-induced calcium entry in isolated cochlear outer hair cells
1Laboratoire d'Audiologie Expérimentale, INSERM unité 229, Université de Bordeaux II, Hôpital Pellegrin, France.
Hearing Research
|November 1, 1991
Summary
Cisplatin (cis-DDP), an ototoxic drug, does not harm outer hair cell viability but blocks calcium entry. This suggests cis-DDP acts as a calcium channel blocker in cochlear cells.
Area of Science:
- Ototoxicology
- Cell Physiology
- Neuroscience
Background:
- Cisplatin (cis-DDP) is a chemotherapy drug known for its ototoxic side effects.
- Outer hair cells (OHCs) are crucial for hearing sensitivity and function.
- Understanding the cellular mechanisms of cisplatin's ototoxicity is vital for mitigating hearing loss.
Purpose of the Study:
- To investigate the acute effects of cisplatin (cis-DDP) on the physiology of isolated cochlear outer hair cells (OHCs).
- To determine if cis-DDP affects OHC viability, contractile responses, or calcium ion influx.
Main Methods:
- Isolated cochlear outer hair cells were cultured in vitro.
- Cell viability was assessed after exposure to cis-DDP.
- Contractile responses were measured using ionomycin stimulation.
- Calcium entry was monitored following [K+]-depolarization in the presence of cis-DDP.
Main Results:
- Cisplatin (cis-DDP) at 1 mM did not affect OHC viability during short-term culture (up to 6 hours).
- cis-DDP (1 mM) did not inhibit ionomycin-induced OHC contractile responses.
- cis-DDP blocked calcium entry evoked by [K+]-depolarization with an IC50 of 45 +/- 30 microM.
Conclusions:
- Cisplatin (cis-DDP) does not acutely impair outer hair cell viability or function.
- cis-DDP acutely inhibits calcium influx in OHCs, suggesting a role as a calcium channel blocker.
- This calcium channel blocking action may contribute to the ototoxic effects of cisplatin.