title: Antiarrhythmic effects and potential mechanism of WenXin KeLi in cardiac Purkinje cells.
abstract: BACKGROUND
  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 (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.
  
  
  CONCLUSIONS
  WXKL exhibits antiarrhythmic properties in cardiac PCs via selective inhibition of I(NaL).
authors.affiliation: Department of Cardiology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Hou
authors.affiliation: Department of Cardiology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Cardiology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi-He
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Li
authors.affiliation: Buchang Cardio-cerebrovascular Hospital, Xian, China.
authors.forename: Bu-Chang
authors.initials: BC
authors.lastname: Zhao
authors.affiliation: Buchang Cardio-cerebrovascular Hospital, Xian, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yue-Peng
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China,. Electronic address: drliyigang@outlook.com.
authors.forename: Yi-Gang
authors.initials: YG
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits
chemical_list: D004365:Drugs, Chinese Herbal; C532373:wenxin keli
keywords: Antiarrhythmic drugs; Cardiac Purkinje cells; Electrophysiology; Late sodium current; WenXin KeLi