顺铂对小鼠耳蜗螺旋神经节细胞延迟整流钾电流的影响

Effect of cisplatin on potassium channel current of murine spiral ganglion neuron

目的探讨耳毒性药物顺铂对耳蜗螺旋神经节细胞延迟整流钾电流的影响,了解顺铂耳毒性的离子机制。方法选择状态良好培养2～14d的耳蜗螺旋神经节细胞在电压钳制条件下记录的钾电流作为对照组,浴液中分别加入100,500,1000,5000μM不同浓度的顺铂溶液后记录的电流为实验组,观察其对钾通道电流电生理学特性的影响,并观察冲洗后电流的恢复情况。结果实验显示耳蜗螺旋神经节细胞钾通道电流的电生理学特性受不同浓度顺铂溶液的影响,并具有浓度依赖性,表现在其活化动力学和电流幅度的改变。本实验中顺铂的50%的电流被抑制时的浓度(IC50)为294μM,冲洗后钾通道电流逐渐恢复。结论顺铂可以改变耳蜗螺旋神经节细胞钾通道电流的电生理学特性,这种变化在短期内可逆,揭示其耳毒性的形成具有一定的离子机制。

Objective To identify the ionic mechanism of ototoxicity of cisplatin by studing the effect of cisplatin on potassium current. Methods Cisplatin solutions of different concentrations （100, 500, 1000, 5000 p,M ） were separately added to the bash solution to study the effect of cisplatin on electrophysiological characteristics of the potassium channel in spiral ganglion neurons after potassium current was recorded. The recovery course was observed when the drag was washed out. Results The electrophysiological properties of potassium channel current were affected by eisplatin solutions in a concentration dependant manner. The changes of clectrophysiological properties showed dynamics in activation and current amplitude with an IC50 of 294 μM. The potassium channel current was recovered gradually ＇after the drug was washed out. Conclusion Cisplatin can change eleetrophysiologieal characteristics of the potassium current in spiral ganglion neurons, which is reversible in a short period of time. This indicates that certain ionic mechanism is involved in the ototoxieity of eisplatin.