کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2921847 | 1175807 | 2016 | 10 صفحه PDF | دانلود رایگان |
BackgroundPrevious 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.ObjectiveTo explore the antiarrhythmic property of WXKL in cardiac Purkinje cells (PCs).MethodsPCs 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).ResultsWXKL (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 (INaL), peak sodium current (INaP), and L-type calcium currents (ICaL) in PCs. WXKL-attenuated ATX-II (5 nM) induced INaL augmentation and blocked INaL with an IC50 of 4.3 ± 0.5 g/L, which is 3- to 4-fold more selective than that of INaP (13.3 ± 0.9 g/L) and ICaL (17.6 ± 1.4 g/L). Moreover, WXKL exerted significantly less use-dependent block of INaP than that of flecainide, indicating its lower proarrhythmic effect.ConclusionsWXKL exhibits antiarrhythmic properties in cardiac PCs via selective inhibition of INaL.
Journal: Heart Rhythm - Volume 13, Issue 4, April 2016, Pages 973–982