title: Inhibitory effects of tetrandrine on the Na(+) channel of human atrial fibrillation myocardium.
abstract: OBJECTIVE
  Tetrandrine (Tet) is a Ca(2+) channel blocker and has antiarrhythmic effects. Less information exists with regard to the mechanisms underlying its antiarrhythmic action other than blocking Ca(2+) channels. In this study, the effects of Tet on the Na(+) current (I(Na)) in the atrial myocardium of patients in atrial fibrillation (AF) and sinus rhythm (SR) were investigated, and the characteristics of the Na(+) current were synchronously compared between the AF and SR patients.
  
  
  METHODS
  Na(+) currents were recorded using the whole-cell patch clamp technique in single atrial myocyte of the AF and the normal SR groups. The effects of Tet (40-120 micromol/L) on the Na(+) current in the two groups were then observed.
  
  
  RESULTS
  Tet (60-120 micromol/L) decreased I(Na) density in a concentration-dependent manner and made the voltage-dependent activation curve shift to more positive voltages in the SR and AF groups. After exposure to Tet, the voltage-dependent inactivation curve of I(Na) was shifted to more negative voltages in the two groups. Tet delayed the time-dependent recovery of I(Na) in a concentration dependent manner in both AF and SR cells; however, there were no differences in the effects of Tet on I(Na) density and properties in the two groups. The I(Na) density of AF patients did not differ from that of the SR patients.
  
  
  CONCLUSIONS
  Tet can block sodium channels with slow recovery kinetics, which may explain the mechanisms underlying the antiarrhythmic action of Tet. The decreased conduction velocity (CV) in AF patients is not caused by the Na(+) current.
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Qi-Yong
authors.initials: QY
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhong-Wen
authors.initials: ZW
authors.lastname: Li
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Zeng
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy*; D044182:Benzylisoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D000889:Anti-Arrhythmia Agents; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D015222:Sodium Channels; C009438:tetrandrine