摘要
目的 研究地西泮对交感神经节细胞钠通道电流的抑制作用机制。方法 酶消化法急性分离SD大鼠(7～ 10d)颈上交感神经节细胞 ,全细胞膜片钳技术记录地西泮对钠通道电流的影响。结果 在钳制电压 (Vh) - 80mV ,刺激电压 (Vt) 0mV条件下 ,0 .3μmol·L- 1地西泮使钠电流峰值降低 14 .76 %(P <0 .0 1) ,其抑制作用与浓度呈正相关 (r =0 .99,P <0 .0 1) ,IC50 为 6 .0 6 μmol·L- 1;钳制电位不同 ,抑制作用也不同 (P <0 .0 5 ) ,Vh- 6 0mV时的IC50 为4 .6 0 μmol·L- 1。 3.0 μmol·L- 1的地西泮使电流 电压曲线峰值平均降低 4 8.94 % ,峰值向去极化方向移动约 10mV ;对激活曲线无明显的影响 (P >0 .0 5 ) ,用药前、后 5 0 %的通道激活时的去极化电压 (V1/2 )分别为 :- 2 4 .6 4mV、 - 2 3.75mV ;3.0 μmol·L- 1的地西泮使稳态失活曲线产生明显的超极化方向移动 (2 0 .12mV ,P <0 .0 1) ,用药前、后 5 0 %的通道灭活时的条件脉冲电压 (V1/2 )分别为 :- 6 4.13mV、- 84 .2 5mV。结论 地西泮对交感神经节细胞钠通道电流有明显的抑制作用 ,且呈浓度及电压依赖性 ;其抑制作用主要与优先结合钠通道的失活状态而影响钠通道的失活有关。
Aim The effects of diazepam on the whole cell sodium currents in rat sympathetic ganglion neurons were studied to investigate the mechanisms by diazepam mediates hypotension. Methods Whole cell patch clamp recordings were performed on enzymatically isolated rat superior cervical sympathetic ganglion neurons. Results Diazepam dose dependently blocked the whole cell sodium currents. Under a V t of 0 mV and a V h of 80 mV 0.3 μmol·L -1 diazepam reduced sodium peak currents by 14.76 %(P< 0.01 ), with a mean IC 50 values of 6.06 μmol·L -1 (r= 0.99 , P< 0.01 ); The blockade was also potential dependent (P< 0.05 ), under a holding potential of 60 mV , the mean IC 50 value was 4.60 μmol·L -1 , 3.0 μmol·L -1 diazepam reduced the peak values of I V curve by 48.94 % and caused 10 mV shift of I V curve to depolarized potentials, a 0.89 mV shift of voltage dependent activation curve to depolarized potentials (P< 0.05 ) and a 20.12 mV shift of the steady state inactivation curve to more hyperpolarized potentials (P< 0.01 ). Following diazepam administration, the conditioning pulse potential at which half maximal channels were inactivated (V 1/2 ), was changed from -64.13 mV to -84.25 mV and the test potential at which half maximal channels were activated (V 1/2 ), was changed from -24.64 mV to -23.75 mV . Conclusion Clinically relevant concentration of diazepam has a significant inhibition on sympathetic ganglion neurons. This inhibition is dose dependent and potential dependent and relevant to the inactivation of sodium channel. The circulation depression of diazepam may be relevant to the direct suppression of sympathetic ganglion neurons.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2001年第2期107-111,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
上海市医学领先专业重点学科基金资助项目
关键词
地西泮
交感神经节
钠通道
膜片钳
diazepam
sympathetic ganglion
sodium channel
patch clamp
