龚冬梅, 单宏丽, 周宇宏, 董德利, 杨宝峰. 哇巴因和乌头碱诱发豚鼠和大鼠心律失常的离子作用靶点哇巴因和乌头碱诱发豚鼠和大鼠心律失常的离子作用靶点J. 药学学报, 2004, 39(5): 328-332.
引用本文: 龚冬梅, 单宏丽, 周宇宏, 董德利, 杨宝峰. 哇巴因和乌头碱诱发豚鼠和大鼠心律失常的离子作用靶点哇巴因和乌头碱诱发豚鼠和大鼠心律失常的离子作用靶点J. 药学学报, 2004, 39(5): 328-332.
GONG Dong-mei, SHAN Hong-li, ZHOU Yu-hong, DONG De-li, YANG Bao-feng. The ion targets of arrhythmias induced by ouabain and aconitine in guinea pig and rat ventricular myocytesJ. Acta Pharmaceutica Sinica, 2004, 39(5): 328-332.
Citation: GONG Dong-mei, SHAN Hong-li, ZHOU Yu-hong, DONG De-li, YANG Bao-feng. The ion targets of arrhythmias induced by ouabain and aconitine in guinea pig and rat ventricular myocytesJ. Acta Pharmaceutica Sinica, 2004, 39(5): 328-332.

哇巴因和乌头碱诱发豚鼠和大鼠心律失常的离子作用靶点哇巴因和乌头碱诱发豚鼠和大鼠心律失常的离子作用靶点

The ion targets of arrhythmias induced by ouabain and aconitine in guinea pig and rat ventricular myocytes

  • 摘要: 目的观察哇巴因和乌头碱对豚鼠和大鼠心肌单细胞离子通道的作用,确定两药诱发心律失常时离子靶点和最佳靶点,建立细胞水平的心律失常模型。方法用全细胞膜片钳技术记录哇巴因和乌头碱对酶解法分离的豚鼠和大鼠心肌细胞离子通道的作用。结果5 μmol·L-1哇巴因使豚鼠心肌细胞APD延长、ICa-L增加、Ik减少、Ik1减少;1 μmol·L-1乌头碱使大鼠心肌细胞APD延长、ICa-L增加、Ito减少、Ik1增加。结论哇巴因和乌头碱诱发心律失常的离子靶点有APD,ICa-L,Ik,ItoIk1,而最佳靶点应为APD,ICa-L,IkIto。在单细胞水平分别应用哇巴因和乌头碱诱发豚鼠和大鼠心律失常,具有稳定性高、条件可控、重复性好等优点,可用于药物筛选和机制研究。

     

    Abstract: AimTo observe the effects of ouabain and aconitine on APD and ion channels in isolated guinea pig and rat ventricular myocytes; to elucidate the action mechanisms of these two drugs and set up new arrhythmic models on cellular level. MethodsIn isolated ventricular myocytes of guinea pig and rat, the effects of ouabain and aconitine on APD, ICa-L, Ik, Ito and Ik1 were observed using the whole cell patch clamp technique. ResultsOuabain (5 μmol·L-1) obviously prolonged the APD90, increased ICa-L, decreased Ik and Ik1 in guinea pig ventricular myocytes. Aconitine (1 μmol·L-1) lengthened the APD90, increased ICa-L, decreased Ito and increased Ik1 in rat ventricular myocytes. ConclusionThe targets on ouabain- and aconitine-induced arrhythmias included APD, ICa-L, Ik, Ito and Ik1. APD, ICa-L, Ik and Ito must be the powerful ones, both in arrhythmic and antiarrhythmic courses. The ouabain- and aconitine- induced arrhythmic models on cellular level were built to study the antiarrhythmic mechanisms of chemicals and evaluate new drugs. These two new-type models in vitro were stable, liable, repeatable and economic, which were superior to those typical models in vivo.

     

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