脱氧鬼臼毒素对大鼠背根神经元电压依赖性钾通道的作用

The effects of deoxypodophyllotoxin on voltage-dependant K^+ channels of rat dorsal root ganglion(DRG) neurons

目的:探讨脱氧鬼臼毒素(DOP)对外周神经系统的毒性作用机制。方法:采用全细胞膜片钳技术研究DOP对急性分离大鼠背根(DRG)神经元电压依赖性钾通道的作用,从离子通道水平探讨其神经毒性作用机制。结果:10、20、40、80μmol/L的DOP对全钾电流(IK)和延迟整流钾电流(IKDR)均有影响,且能以浓度依赖方式、部分可逆地阻断电压依赖性钾电流,使电流电压曲线向去极化方向移动。同时,DOP对IKDR的抑制率[(43.22±6.85)%]明显高于IK[(27.55±4.65)%]。结论:DOP对钾离子电流的影响可能是鬼臼毒素类化合物引起外周神经病变的机制之一。

Objective:To investigate the mechanism of deoxypodophyllotoxin(DOP) against the peripheral nervous system.Methods: The effects of DOP on voltage-dependant K+ channels were studied by using whole-cell patch-clamp recordings on acute isolated rat dorsal root ganglion(DRG) neurons.Results: DOP can reversibly block voltage-dependent potassium current(IK) and delayed-rectifier potassium current(IKDR) and make the curve of the current-voltage relation shift to positive potentials at the concentration of 10,20,40 and 80 μmol/L.This study thus demonstrated that DOP is a dose-dependant and reversibly blocker of IK and IKDR in DRG neurons.The inhibition rate of DOP on IKDR was higher than on IK.Conclusion: It can be concluded that the effect of DOP on the current of potassium channel of DRG neurons may be a possible contributing mechanism for the toxin on peripheral nervous system.