加巴喷丁对急性分离大鼠三叉神经节神经元高电压激活钙电流的影响

Effects of gabapentin on high-threshold calcium currents in acute dissociated trigeminal ganglion neurons of rats

目的:评价加巴喷丁对急性分离大鼠三叉神经节神经元高电压激活钙电流的影响。方法:清洁级SD雄性大鼠,150～200 g,酶消化急性分离双侧三叉神经节神经元,采用全细胞膜片钳技术记录三叉神经节神经元高电压激活钙电流。记录加巴喷丁10、30、100μmol/L(G1-3组,n=10)作用下的钙电流,计算电流抑制率;并绘制浓度依赖曲线和100μmol/L加巴喷丁作用下钙电流-电压曲线、钙通道激活曲线和稳态失活曲线。计算半数激活电压和半数失活电压。结果:加巴喷丁(10、30、100μmol/L)均能抑制三叉神经节神经元钙电流(P<0.05),且抑制率随浓度增加而增大(P<0.05)。加入100μmol/L加巴喷丁后,钙电流峰值降低,激活曲线和稳态失活曲线分别向超极化方向移动,半数激活电压和半数失活电压均降低(P<0.05),且稳态失活曲线移动程度大于激活曲线。结论:加巴喷丁能够抑制三叉神经节神经元高电压激活钙电流,可能与其主要改变钙通道失活动力学特征有关。该作用可能为加巴喷丁治疗三叉神经痛作用机制之一。

Objective： To investigate the effect of gabapentin on high voltage active calcium currents in acute dissociated trigeminal ganglion neurons of rat.Methods： Pathogen-free male SD rats weight 150~200 g were used in this study.The animals were decapitated after being anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg.Bilateral trigeminal ganglion was isolated and the neurons in the ganglion were enzymatically dissociated.The high voltage active calcium current was recorded using whole cell patch clamp technique.Results： Gabapentin（10,30,100 μmol/L） could inhibit the peak calcium current（Ica） in the neurons.The inhibitory effect of 100 μmol/L gabapentin was more significant than the other low concentration groups.Peak Ica was decreased by gabapentin 100 μmol/L and both activation and steady-state inactivation curve shifted to more hyperpolarized potentials.The degree of shift of steady-state inactivation curve was more significant than the one of activation curve.Conclusion： Gabapentin can inhibit high voltage active Ica in the trigeminal ganglion neurons.The alteration in the electrophysiological properties of inactivation may be involved in the mechanism.This may be the possible mechanism of the treatment effect of gabapentin on the primary trigeminal neuralgia.