Department of Physiology, Institute of Medical Science, Kangwon National University School of Medicine, Chuncheon 200-701, Korea.
Korean J Physiol Pharmacol. 2010 Jun;14(3):119-25. doi: 10.4196/kjpp.2010.14.3.119. Epub 2010 Jun 30.
We investigated the effects of a hot-water extract of Artemisia iwayomogi, a plant belonging to family Compositae, on cardiac ventricular delayed rectifier K(+) current (I(K)) using the patch clamp technique. The carbohydrate fraction AIP1 dose-dependently increased the heart rate with an apparent EC(50) value of 56.1+/-5.5 microg/ml. Application of AIP1 reduced the action potential duration (APD) in concentration-dependent fashion by activating I(K) without significantly altering the resting membrane potential (IC(50) value of APD(50): 54.80+/-2.24, IC(50) value of APD(90): 57.45+/-3.47 microg/ml). Based on the results, all experiments were performed with 50 microg/ml of AIP1. Pre-treatment with the rapidly activating delayed rectifier K(+) current (I(Kr)) inhibitor, E-4031 prolonged APD. However, additional application of AIP1 did not reduce APD. The inhibition of slowly activating delayed rectifier K(+) current (I(Ks)) by chromanol 293B did not change the effect of AIP1. AIP1 did not significantly affect coronary arterial tone or ion channels, even at the highest concentration of AIP1. In summary, AIP1 reduces APD by activating I(Kr) but not I(Ks). These results suggest that the natural product AIP1 may provide an adjunctive therapy of long QT syndrome.
我们研究了菊科植物艾草热水提取物对心室延迟整流钾电流(I(K))的影响,采用膜片钳技术。碳水化合物 AIP1 剂量依赖性地增加心率,其表观 EC(50)值为 56.1+/-5.5 microg/ml。AIP1 以浓度依赖性方式激活 I(K),从而缩短动作电位时程(APD),而对静息膜电位无明显影响(APD(50)的 IC(50)值:54.80+/-2.24,APD(90)的 IC(50)值:57.45+/-3.47 microg/ml)。基于这些结果,所有实验均使用 50 microg/ml 的 AIP1 进行。快速激活延迟整流钾电流(I(Kr))抑制剂 E-4031 预处理可延长 APD。然而,额外应用 AIP1 并不能进一步降低 APD。chromanol 293B 抑制缓慢激活延迟整流钾电流(I(Ks))不会改变 AIP1 的作用。AIP1 对冠状动 脉张力或离子通道没有明显影响,即使在 AIP1 的最高浓度下也是如此。总之,AIP1 通过激活 I(Kr)而不是 I(Ks)来缩短 APD。这些结果表明,天然产物 AIP1 可能为长 QT 综合征提供辅助治疗。