title: Distinctive property and pharmacology of voltage-gated sodium current in rat atrial vs ventricular myocytes.
abstract: BACKGROUND
  Several mammalian species display distinct biophysical properties between atrial and ventricular voltage-gated sodium current (INa); however, the potential mechanism behind this phenomenon is unknown.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the potential molecular identities of the different INa in atrial and ventricular myocytes of rat hearts.
  
  
  METHODS
  Whole-cell patch voltage-clamp and molecular biology techniques were used in the study.
  
  
  RESULTS
  Ventricular INa exhibited a slower inactivation, more positive potential of inactivation, and quicker recovery from inactivation compared to atrial INa. Real-time polymerase chain reaction and western blot analysis revealed that mRNA and protein levels of NaVβ2 and NaVβ4 subunits, but not NaV1.5, were greater in ventricular myocytes than in atrial myocytes. INa in heterologous HEK 293 cell expression system with coexpressing hNaV1.5 and hNaVβ2/hNaVβ4 showed similar biophysical properties to ventricular INa. Greater protein expression of NaVβ2 and NaVβ4 subunits was also observed in human ventricles. Interestingly, pharmacologic study revealed that the antiarrhythmic drug dronedarone (10 μM) inhibited atrial INa more (by 73%) than ventricular INa (by 42%), and shifted its inactivation to more negative voltages (-4.6 mV) compared to ventricular INa.
  
  
  CONCLUSIONS
  The results of this study demonstrate the novel information that the distinctive biophysical properties of INa in atrial and ventricular myocytes can be attributed to inhomogeneous expression of NaVβ2 and NaVβ4 subunits, and that atrial INa is more sensitive to inhibition by dronedarone.
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China; Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Kui-Hao
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Xu
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Department of Cardiac Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xin-Ling
authors.initials: XL
authors.lastname: Du
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China; Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China; Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, China.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Xiao
authors.affiliation: Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: mwjin@mail.tjmu.edu.cn.
authors.forename: Man-Wen
authors.initials: MW
authors.lastname: Jin
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China; Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, China. Electronic address: grli8@outlook.com.
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Li
mesh_terms: D000638:Amiodarone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000077764:Dronedarone; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000187:drug effects / Q000378:metabolism*
chemical_list: D026941:Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D000077764:Dronedarone; D000638:Amiodarone
keywords: Cardiac myocytes; Distinctive properties of atrial and ventricular I(Na); Dronedarone; Voltage-gated sodium current