Antiarrhythmic Effects And Potential Mechanism Of WenXin KeLi In Cardiac Purkinje Cells

BACKGROUND Previous studies have demonstrated that WenXin KeLi?WXKL?,a traditional Chinese medicine can exert antiarrhythmic property through complex multichannel inhibition,but its pharmacological effect remains to be elucidated,especially in 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.ATX-II and isoproterenol?ISO?were used to induce early or delayed afterdepolarizations?EADs,DADs?or triggered activities?TAs?.RESULTS WXKL?1g/L and 5g/L?significantly abbreviated the action potential duration?APD?of PCs in a dose and rate dependent manner.Treatment of PCs with ATX-II?2nM?prolonged APD and induced EADs,which were significantly suppressed by WXKL.WXKL?1,5g/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?5nM?induced I_NaL augmentation and blocked I_NaL with an IC₅₀ of 4.3±0.5g/L,which is 3 to 4 fold more selective than that of I_NaP?13.3±0.9g/L?and I_CaL?17.6±1.4g/L?.Moreover,WXKL exert significantly less use-dependent block of I_NaP than that of flecainide,indicating its lower proarrhythmic effect.CONCLUSIONS WXKL exhibits antiarrhythmic property in cardiac PCs via selective inhibition of INaL.