盐酸关附甲素对豚鼠和大鼠心肌细胞钾通道的阻断作用

目的用膜片钳全细胞记录法观察盐酸关附甲素(GFA)对分离的单个豚鼠心室肌细胞缓慢激活型延迟整流钾电流(IKs),大鼠内向整流钾电流(IK1)、瞬时外向钾电流(Ito)的影响。方法用急性酶解法分离获得单个豚鼠和大鼠心室肌细胞。用标准的全细胞膜片钳技术记录IKs、IK1、Ito离子通道电流,观察不同浓度的GFA对豚鼠心室肌细胞IKs,大鼠心室肌细胞IK1、Ito的影响。结果50,150,500μmol/LGFA使IKs尾电流(IKs,tail)最大峰值电流密度分别降低11.4%±3.32%、23.3%±7.36%、36.7%±4.99%,P<0.05;使IK1稳态电流密度分别降低5.1%±0.6%、7.5%±0.9%、7.2%±0.9%;50,500μmol/LGFA使Ito最大峰值电流密度分别降低6.1%±0.64%、8.6%±1.13%。结论GFA对IKs具有浓度依赖性阻滞作用,这可能是其延长动作电位时程而对静息电位影响不大的电生理基础,是其抗心律失常作用的机制之一。

Blocking effects of Guanfu base A on potassium current in isolated rat and guinea pig ventricular myocytes

Objective The effects of Guanfu base A (GFA) on slow activating delayed rectifier potassium current (I_ Ks ),inward rectifier potassium current (I_ K1 )and transient outward potassium(I_ to ) were evaluated in isolated ventricular myocytes of guinea pigs and rats. Methods Single ventricular cell was obtained from healthy guinea pig and rat hearts using enzymatic dissociation technique. The whole cell patch clamp method was used to record the I_ Ks ,I_ K1 and I_ to . Results GFA(50,150,500μmol/L) produced a concentration-dependent reduction of I_ Ks,tail by 11.4%±3.32%,23.3%±7.36%, 36.7%±4.99% from control(P<0.05). ② GFA (50,150,500μmol/L) decreased the I_ K1 by 5.1%±0.6%, 7.5%±0.9 %,7.2%±0.9% from control. GFA (50, 500μmol) decreased the I_ to by 6.1%±0.64%, 8.6%±1.13%from control. Conclusions GFA can inhibit I_ Ks,tail in a concentration-dependent manner and slightly inhibit I_ K1 and I_ to which might explain its effects of prolonging duration of action potention. It may be one of the major mechanisms of its antiarrhythmic action.