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KMID : 0858620030070010032
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Korean Journal of Audiology
2003 Volume.7 No. 1 p.32 ~ p.37
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The Effect of Cisplatin on the Calcium Regulation in Isolated Outer Hair Cells of Guinea Pig
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Chung Jong-Woo
Kang Hun-Hee
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Abstract
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The mechanism of cisplatin ototoxicity has been studied and there found several evidences of outer hair cell damage. Calcium plays an important role in cellular signal transduction and many studies argued that calcium channel was blocked or modified by ototoxic drug. In this study, authors aimed to know the intracellular calcium regulation by cisplatin in isolated outer hair cells and to speculate the mechanism of hearing loss by cisplatin. Outer hair cells were isolated from guinea pig by enzymatic and mechanic dissociation. Intracellular calcium was measured by Fura 2-AM fluorescent dye. Cisplatin solution (0.3 mM) was perfused in bath solution and the changes of the intracellular calcium were recorded. High-potassium induced increase of intracellular calcium ([Ca2+]i) was partially inhibited by cisplatin but repeated perfusion of cisplatin could increase [Ca2+]i even after the perfusion of nifedipine. In the absence of external calcium, [Ca2+]i was not changed by adding cisplatin to bath solution, but when the outer hair cells were perfused with 1 mM calcium bath solution including 0.3 mM cisplatin, [Ca2+]i increased. After preincubation of outer hair cells with 3 mM verapamil, cisplatin did not induce the [Ca2+]i increase in the presence of external calcium. And when the cells were perfused with 1 mM Ca2+ and cisplatin, [Ca2+]i started to increase. From this study, we could conclude that cisplatin deteriorate intracellular calcium regulation in outer hair cells and induce the cells dead.
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KEYWORD
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Calcium ion, Cisplatin ototoxicity, Fura-2, Signal transduction mechanism
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