氧化苦参碱对大鼠海马神经元细胞钠通道的影响

Effects of oxymatrine on sodium channels in cultured rat hippocampal neurons

目的 研究氧化苦参碱（oxymatrine，OMT）对培养的新生大鼠海马神经元细胞膜钠电流作用，探讨OMT在离子通道水平的作用机制。方法 采用原代培养新生大鼠海马神经元细胞，应用全细胞膜片钳技术，观察不同浓度OMT对培养8～12天的大鼠海马神经元细胞膜钠通道的作用。结果 OMT对海马神经元细胞膜钠电流有明显的抑制作用（n=20，P〈0．05），且这种作用具有浓度依赖性，OMT对钠电流作用的半数抑制浓度为（46．1±1．3）μmol／L。在30μmol／L时，OMT可使钠电流Ⅰ-Ⅴ曲线显著上移，并且改变钠电流的翻转电位，但不影响激活电位和峰电位。通道动力学显示OMT可以促进钠电流复活曲线向右移动，减慢通道由失活状态恢复到激活状态的过程，但对激活曲线和失活曲线则没有明显的作用。结论 OMT呈浓度依赖性和电压依赖性抑制大鼠海马神经元细胞膜钠电流，并且抑制钠通道的复活过程。

Objective To investigate effects of oxymatrine （OMT） on sodium channels in cultured rat hippocampal neurons. Methods The whole cell patch clamp technique was employed to study effects of various concentrations of OMT on sodium currents recorded in primary cultured rat hippocampal neurons. Results Sodium currents were significantly inhibited by OMT in a concentration-dependent manner. Concentration-effects analysis of these effects showed the IC50 value of OMT on sodium current was （46.1±1.3）μmol/L （ n = 20, P 〈 0.05）. 30μmol/L of OMT markedly moved Ⅰ-Ⅴ curve up and affected the reverse potential, but didn＇ t affect the activation potential and peak potential of sodium currents. Channel kinetic data showed that OMT significantly shifted the time-dependent recovery curve of sodium currents to the right, but did not alter the inactivation curve and the activation curve. Conclusion OMT markedly reduces sodium currents in a concentrationdependent and voltage-dependent manner, which is involved in slowing down the recovery curve of sodium currents by OMT in cultured rat hippoeampal neurons.