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[钙拮抗剂对内耳保护作用的直接证据。抑制豚鼠毛细胞内钙水平的毒性升高]

[Direct evidence of a protective effect of calcium antagonists on the inner ear. Inhibition of a toxic increase in the calcium level in hair cells of the guinea pig].

作者信息

Nilles R

机构信息

Universitäts-HNO-Klinik Tübingen.

出版信息

HNO. 1995 Dec;43(12):716-23.

PMID:8582831
Abstract

Calcium is considered to be a second messenger after the transduction process in outer hair cells and is needed in combination with actin and myosin for slow cell motility. In analogy to the myocardium, abnormal increases in intracellular (Ca2+) are believed to lead to cell death by the activation of calcium-sensitive proteases and phospholipases. Calcium overloading can be created by a high extracellular potassium medium. In the present study we incubated isolated outer hair cells from the guinea pig in Hank's medium with and without the calcium channel antagonists verapamil chloride, flunarizin and nifedipine in concentrations from 10(-9) M to 10(-4) M. We measured a calcium increase using the (FURA-2) method after an increase in extracellular potassium. In the same experiment we also measured the survival time of isolated outer hair cells. The results showed that calcium increases could be reduced significantly in the presence of calcium antagonists. We also showed that survival time could be significantly prolonged. Our conclusions are that a protective effect of the calcium channel blockers exists for outer hair cells, and this effect is probably due to the presence of voltage-sensitive calcium channels of the L-type in the cell membrane.

摘要

钙被认为是外毛细胞转导过程后的第二信使,并且在细胞缓慢运动中与肌动蛋白和肌球蛋白结合时是必需的。与心肌类似,细胞内(Ca2+)异常增加被认为会通过激活钙敏感性蛋白酶和磷脂酶导致细胞死亡。高细胞外钾培养基可导致钙超载。在本研究中,我们将豚鼠分离的外毛细胞在含有和不含有浓度为10(-9)M至10(-4)M的钙通道拮抗剂维拉帕米、氟桂利嗪和硝苯地平的Hank's培养基中孵育。在细胞外钾增加后,我们使用(FURA-2)方法测量钙的增加。在同一实验中,我们还测量了分离的外毛细胞的存活时间。结果表明,在存在钙拮抗剂的情况下,钙的增加可显著降低。我们还表明存活时间可显著延长。我们的结论是,钙通道阻滞剂对外毛细胞存在保护作用,并且这种作用可能是由于细胞膜中存在L型电压敏感性钙通道。

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