顺铂可阻断离体耳蜗外毛细胞中去极化诱导的钙内流。

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

作者信息

Saito T, Moataz R, Dulon D

机构信息

Laboratoire d'Audiologie Expérimentale, INSERM unité 229, Université de Bordeaux II, Hôpital Pellegrin, France.

出版信息

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

DOI:10.1016/0378-5955(91)90163-4

PMID:1663104

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.

摘要

研究了耳毒性分子顺铂（cis-DDP）对离体耳蜗外毛细胞生理功能的影响。即使在1 mM的高浓度下，顺铂也不会影响体外短期培养（细胞解离后6小时是测试的最长时间）的外毛细胞的活力。此外，1 mM顺铂的存在也不会抑制通过外部施加钙离子载体离子霉素刺激外毛细胞产生的收缩反应。然而，顺铂能够阻断由[K+]去极化引起的钙内流，剂量抑制曲线表明其半数抑制浓度（IC50）为45±30 microM。这些结果表明，顺铂对外毛细胞生理功能的急性作用之一可能发生在质膜水平，在那里它作为一种Ca(2+)通道阻滞剂发挥作用。