Department of Cardiology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Buchang Cardio-cerebrovascular Hospital, Xian, China.
Heart Rhythm. 2016 Apr;13(4):973-82. doi: 10.1016/j.hrthm.2015.12.023. Epub 2015 Dec 14.
Previous studies have demonstrated that WenXin KeLi (WXKL), a traditional Chinese medicine, can exert antiarrhythmic properties through complex multichannel inhibition, but its pharmacologic effect remains to be elucidated, especially in the cardiac conductive system.
To explore the antiarrhythmic property of WXKL in cardiac Purkinje cells (PCs).
PCs were isolated from rabbit hearts and action potentials (APs) and ion currents were recorded by whole-cell patch clamp technique. Anemonia toxin II (ATX-II) and isoproterenol (ISO) were used to induce early or delayed afterdepolarizations (EADs, DADs) or triggered activities (TAs).
WXKL (1 g/L and 5 g/L) significantly abbreviated the action potential duration (APD) of PCs in a dose- and rate-dependent manner. Treatment of PCs with ATX-II (2 nM) prolonged APD and induced EADs, which were significantly suppressed by WXKL. WXKL (1, 5 g/L) also inhibited ISO-induced EADs, DADs, and TAs. To reveal the ionic mechanisms, we studied the effects of WXKL on late sodium current (I(NaL)), peak sodium current (I(NaP)), and L-type calcium currents (ICaL) in PCs. WXKL-attenuated ATX-II (5 nM) induced I(NaL) augmentation and blocked I(NaL) with an IC50 of 4.3 ± 0.5 g/L, which is 3- to 4-fold more selective than that of I(NaP) (13.3 ± 0.9 g/L) and ICaL (17.6 ± 1.4 g/L). Moreover, WXKL exerted significantly less use-dependent block of I(NaP) than that of flecainide, indicating its lower proarrhythmic effect.
WXKL exhibits antiarrhythmic properties in cardiac PCs via selective inhibition of I(NaL).
既往研究表明，稳心颗粒（WXKL）是一种中药，通过多通道抑制作用发挥抗心律失常作用，但具体的药理作用仍有待阐明，特别是在心脏传导系统。
探讨 WXKL 对心脏浦肯野纤维（PCs）的抗心律失常作用。
采用全细胞膜片钳技术，从兔心中分离 PC，记录动作电位（AP）和离子电流。应用海兔毒素 II（ATX-II）和异丙肾上腺素（ISO）诱导早期后除极（EAD）、延迟后除极（DAD）或触发活动（TA）。
WXKL（1 g/L 和 5 g/L）呈浓度和频率依赖性地缩短 PC 的动作电位时程（APD）。用 2 nM ATX-II 处理 PC 可延长 APD 并诱发 EAD，WXKL 可显著抑制 EAD。WXKL（1、5 g/L）还抑制 ISO 诱导的 EAD、DAD 和 TA。为了揭示离子机制，我们研究了 WXKL 对 PC 中的晚期钠电流（I(NaL)）、峰值钠电流（I(NaP)）和 L 型钙电流（ICaL）的影响。WXKL 可减弱 5 nM ATX-II 诱导的 I(NaL)增强，并以 4.3 ± 0.5 g/L 的 IC50 阻断 I(NaL)，对 I(NaL)的选择性是 I(NaP)（13.3 ± 0.9 g/L）和 ICaL（17.6 ± 1.4 g/L）的 3-4 倍。此外，与氟卡尼相比，WXKL 对 I(NaP)的使用依赖性阻滞作用明显较小，表明其致心律失常作用较低。
WXKL 通过选择性抑制 I(NaL)表现出抗心律失常作用。
