摘要
探讨溴苄基四氢小檗碱 (CPU86 0 35 )对豚鼠心室肌细胞钾离子通道及L 型钙离子通道的作用 ,探讨其抗心律失常的离子通道机制。取 2 0只健康豚鼠 ,雌雄不拘 ,体重 2 5 0~ 30 0g ,双酶法酶解获取单个豚鼠心室肌细胞 ,采取用药前后自身对照及全细胞膜片钳记录方法观察CPU86 0 35对正常豚鼠心室肌细胞延迟整流钾离子流 (IK)、内向整流钾离子流 (IK1)及L 型钙离子流 (ICa L)的影响。结果 :CPU86 0 35对豚鼠单个心室肌细胞IK 呈浓度依赖性抑制作用 ,半数抑制浓度 (ID50 )为 5 6 μmol/L ;CPU86 0 35对IK1无明显影响。CPU86 0 35呈剂量依赖性抑制ICa L,ID50 为 6 5μmol/L。CPU86 0 35对ICa L的抑制依赖于保持电位 (HP) ,HP =- 4 0mV和 - 80mV时 ,75 μmol/LCPU86 0 35对ICa L的抑制率分别为 0 .4 92 2± 0 .0 2 1和 0 .6 377± 0 .0 36 6。结论 :CPU86 0 35对正常豚鼠心室肌细胞IK、及ICa L均有阻断作用 ,这种多离子通道的阻断剂可有效抗快速心律失常 ,并且不会引起动作电位时程和有效不应期的过度延长 ,从而减少药物的致心律失常作用。
To investigate the effects of bromibenzyltetrahydraberberine on delayed rectifier potassium current and inward rectifier potassium current and L-type calcium current in isolated single guinea pig ventricular myocyte. Single ventricular cell was obtained from healthy guinea pig hearts using enzymatic dissociation technique. The whole cell patch clamp method was used to record the delayed rectifier potassium current(I K), the inward rectifier potassium current(I K1), and the L-type calcium current (I Ca-L). Results: Bromibenzyltetrahydraberberine has dose-dependent blocking effects on I K.ID 50 is 56μmol/L. It has no change on I-V shape of I K. It has no obvious effect on I K1. Bromibenzyltetrahydraberberine has dose-dependant blocking effect on I Ca-L .ID 50 is 65μmol/L. The inhibition of bromibenzyltetrahydraberberine on I Ca-L was dependent of the holding potential (HP).75μmol/L bromibenzyltetrahydraberberine inhibited I Ca-L by 0.4922±0.021 at HP=-40 mV, and 0.6377±0.0366 at HP=-80 mV. Conclusion: Bromibenzyltetrahydraberberine can decrease delayed rectifier potassium current and L-type calcium current in single guinea pig ventricular myocyte. It is a muti-ion blocking antirarrhythmia agent.
出处
《中国心脏起搏与心电生理杂志》
2004年第2期116-119,共4页
Chinese Journal of Cardiac Pacing and Electrophysiology