顺铂对大鼠耳蜗螺旋神经节细胞外向延迟整流钾电流的影响

Effect of cisplitin on the potassium channels of spiral ganglion neurons from neonatal rats

目的:观察记录顺铂作用下急性分离新生大鼠耳蜗螺旋神经节细胞(SGNs)延迟整流钾通道的电流曲线,分析顺铂对SGNs钾电流激活动力学的影响,并初步探讨其耳毒性机制。方法:采用全细胞膜片钳技术记录SGNs外向延迟整流钾电流及顺铂对此电流的影响。结果:钳制电压为-60mV,刺激电压从-60mV到+80mV逐渐去极化,阶跃电压为10mV,持续时间为500ms,可在SGNs上记录到外向钾电流,该电流对TEA-Cl(4-乙基胺)敏感,具有延迟整流特性;在细胞外液中加入10μmol/L顺铂,能明显抑制SGNs延迟整流钾电流;顺铂对此电流的抑制作用与细胞外液中顺铂的浓度呈剂量依赖性;外液洗脱后SGNs电流可基本恢复正常。结论:钾通道与SGNs动作电位的产生密切相关,顺铂可抑制SGNs钾通道电流,导致听觉功能障碍。

Objective：To investigate the effect of cisplatin on outward delayed rectifier potassium currents（IKDR currents）in isolated spiral ganglion neurous cells and to analyze possible intracellular mechanism of this effects by using the patch-clamp technique. Method：The IKDR was recorded and measured before and after the application of 10μmol/L cisplatin in external solution by using the whole cell patch-clamp technique, Result： Cisplatin could inhibit SGNs voltage-dependent potassium channels, the zero current potential and reversal potential of IKDR currents were both shift to polarizing directions by 10μmol/L cisplatin, Moreover, the maxinal magnitude of IKDR currents were dicreased by 23.3% when giving the test pulse at ＋50 mY. Cisplatin＇s inhibitation on IKDR has dose-depentence with cisplatin＇concerntration in extracellular fluid and the currents recoverd completely after cisplatin being washed out. Conclusion：This research explained the otoxic mechanism of cisplatin through its action on keeping from spiral ganglion neuron＇s IKDR from the eletrophysiological aspect and set a foundation for further research.