title: Larger rate dependence of late sodium current in cardiac Purkinje cells: A potential link to arrhythmogenesis.
abstract: Purkinje cells (PCs) have a steeper rate dependence of repolarization and are more susceptible to arrhythmic activity than do ventricular myocytes (VMs). Late sodium current (INaL) is rate dependent and contributes to rate dependence of repolarization.
  
  
  
  This study sought to test our hypothesis that PCs have a larger rate dependence of INaL, contributing to their steeper rate dependence of repolarization and higher susceptibility to arrhythmic activity, than do VMs.
  
  
  
  INaLwas recorded in isolated rabbit PCs and VMs with the whole-cell patch clamp technique. Action potential was examined using the microelectrode technique.
  
  
  
  Compared with VMs, PCs exhibited a significantly larger rate dependence of INaLwith a larger INaLto basic cycle length (BCL) slope. Moreover, PCs had a larger rate dependence of INaLdecay and slower recovery kinetics. Interestingly, the larger rate dependence of INaLmatched to a steeper rate dependence of action potential duration (APD) in PCs. The INaLblocker tetrodotoxin significantly blunted, while the INaLenhancer anemone toxin (ATX-II) significantly increased, the rate dependence of INaLand APD in PCs and VMs. In the presence of ATX-II, the rate dependence of INaLin PCs was markedly larger than that in VMs, causing a much steeper rate dependence of APD in PCs. Accordingly, PCs exhibited greater rate-dependent electrical instability and were more prone to ATX-II-induced early afterdepolarizations, which were completely inhibited by the INaLinhibitor ranolazine.
  
  
  
  PCs have a significantly larger rate dependence of INaLthan do VMs because of distinctive INaLdecay and recovery kinetics, which contributes to their larger rate adaptation, and simultaneously predisposes them to a higher risk of arrhythmogenesis.
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: Ying
authors.initials: Y
authors.lastname: Yu
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, Shanghai Xuhui District Central Hospital/Shanghai Clinical Center of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Zhou
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: Peng-Pai
authors.initials: PP
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhi-Quan
authors.initials: ZQ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
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 / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D011817:Rabbits; D061566:Voltage-Gated Sodium Channels / Q000502:physiology*
chemical_list: D061566:Voltage-Gated Sodium Channels
keywords: Action potential duration; Arrhythmogenesis; Late sodium current; Purkinje cell; Rate adaptation; Reverse use dependence