Antiarrhythmic effects and potential mechanism of WenXin KeLi in cardiac Purkinje cells

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• 作者：Jian-Wen Hou ; MD^* ; Wei Li ; MD^* ; Kai Guo ; MD^* ; Xiao-Meng Chen ; MD^* ; Yi-He Chen ; MD^* ; Chang-Yi Li ; MD^* ; Bu-Chang Zhao ; MD^&dagger ; ; Jing Zhao ; MD^&dagger ; ; Hong Wang ; PhD^* ; Yue-Peng Wang ; MD ; PhD^* ; Yi-Gang Li ; MD ; FHRS^* ; ^{drliyigang@outlook.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Antiarrhythmic drugs ; Cardiac Purkinje cells ; Electrophysiology ; WenXin KeLi ; Late sodium current
• 刊名：Heart Rhythm
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：13
• 期：4
• 页码：973-982
• 全文大小：2268 K

文摘

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.

Objective

To explore the antiarrhythmic property of WXKL in cardiac Purkinje cells (PCs).

Methods

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).

Results

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 (I_CaL) 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 I_CaL (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.

Conclusions

WXKL exhibits antiarrhythmic properties in cardiac PCs via selective inhibition of I_NaL.