SO_2衍生物对大鼠神经元和心肌细胞几种离子通道的影响

Effects of SO_2 Derivatives on Ion Channels in Acutely Isolated Rat Neurons and Cardiomyocytes

为了阐明大气污染物SO2对神经系统和心血管系统的毒作用机制,采用全细胞膜片钳技术研究了SO2衍生物(NaHSO3和Na2SO3,分子比为1∶3)对大鼠海马、背根节神经元和心肌细胞膜上钠、钾、钙离子通道的影响.结果显示:(1)SO2衍生物可显著增大大鼠海马CA1区神经元钠电流,不影响钠通道的激活过程,但可使钠电流的失活曲线向去极化方向移动,延迟钠通道的失活过程;另外,SO2衍生物可显著增大瞬间外向钾电流(IA)和延迟整流钾电流(IK),不影响IA的激活过程,使IK的激活过程向负电压方向移动,促进IK的激活过程,而使IA的失活曲线向正电压方向移动,延迟IA的失活过程.(2)SO2衍生物显著增大大鼠背根节神经元钠电流(TTX-S钠电流和TTX-R钠电流),可使两种钠电流的激活和失活曲线均向去极化方向移动,但对失活的影响大于对激活的影响,即延迟钠通道的失活过程;SO2衍生物显著增大背根节神经元瞬间外向钾电流(TOCs)和延迟整流钾电流(IK),不影响TOCs的激活过程,但可使IK的激活曲线向超极化方向移动,促进IK的激活.另外,还可使TOCs的失活曲线向去极化方向移动,即延迟TOCs的失活.(3)SO2衍生物可显著增大大鼠心肌细胞L-型钙电流(ICa,L),使ICa,L的激活和失活曲线均向去极化方向移动,但对失活的影响大于对激活的影响;SO2衍生物显著增大心肌细胞钠电流,不影响钠通道的激活过程,但可使钠电流的失活曲线向去极化方向移动,延迟钠通道的失活过程;SO2衍生物显著增大心肌细胞瞬间外向钾电流(Ito),使Ito的激活曲线向超极化方向移动,促进Ito的激活过程,但可使Ito的失活曲线向去极化方向移动,延迟Ito的失活过程;此外,SO2衍生物还可显著增大心肌细胞内向整流钾电流(IK1),但不影响其反转电位.结果表明,SO2衍生物可能通过影响神经元和心肌细胞膜上离子通道的活动而对中枢神经、传导神经以及心血管系统产生不利影响.提示大气SO2污染可能与神经系统和心血管系统疾病的发生有关.

In order to investigate the toxic mechanisms of SO2, an air pollutant, in neuronal and cardiovascular systerms, the effects of SO2 derivatives （bisulfite and sulfite, 1 ： 3 ） on ionic channels in acutely isolated rat hippocampal neurons, dorsal root ganglion （DRG） neurons and cardiomyocytes were studied using the whole-cell patch clamp technique. SO2 derivatives significantly increased sodium current in hippocampal neurons, shifted its inactivation curve to more positive potential, without affecting the current activation curve. SO2 derivatives aslo significantly increased transient outward potassium current （IA） and delayed rectifier potassium current（ IK ）, shifted the activation curve of IK to more negative potential and the inactivation curve of Is to more positive potential,and without affecting the activation of Is. Sodium currents （TTX-S and TTX-R） in DRG neurons were increased by SO2 derivatives, its activation and inactivation curves were both shifted to more positive potential, but the effect on the latter being more pronounced. Transient outward potassium （TOCs） and delayed rectifier potassium（IK） currents were also increased by SO2 derivatives. The inactivation curve of TOCs was shifted to more positive potential and the activation curve of IK was shifted to more negative potential, but the activation curve of TOCs was not affected by SO2 derivatives. In addition, SO2 derivatives significantly increased L-type calcium current （ICa.L）in cardiomyocytes. The activation End inactivation curves of ICa.L were shifted to more positive potential, but the effect on the latter being more pronounced. SO2 derivatives significantly increased sodium current in cardiomyocytes,shifted its inactivation curve to more positive potential and without affecting the activation curve. The transient outward potassium current （Ito） was also increased by SO2 derivatives, its activation curve was shifted to more negative potential and inactivation curve was shifted to more positive potential. The inward rectifier potassium current （IKI） was increased by SO2 derivatives, but its reversal potential was not changed. These results indicated that SO2 derivatives might cause damages to neuronal and cardiovascular system through affecting the ionic channels in neurons and cardiomyocytes.