Inhibitory effects of tetrandrine on the Na^＋ channel of human atrial fibrillation myocardium

• Published in: Acta pharmacologica Sinica 2009-02, Vol.30 (2), p.166-174
• Main Authors: Chen, Li, Li, Qi-yong, Yang, Yan, Li, Zhong-wen, Zeng, Xiao-rong
• Format: Article
• Language: English
• Subjects: Adult; Anti-Arrhythmia Agents - pharmacology; Anti-Arrhythmia Agents - therapeutic use; Atrial Fibrillation - drug therapy; Benzylisoquinolines - pharmacology; Benzylisoquinolines - therapeutic use; Biomedical and Life Sciences; Biomedicine; Calcium Channel Blockers - pharmacology; Calcium Channel Blockers - therapeutic use; Female; Heart - drug effects; Humans; Immunology; Internal Medicine; Ion Channel Gating - drug effects; Male; Medical Microbiology; Middle Aged; Myocardium - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Original; original-article; Patch-Clamp Techniques; Pharmacology/Toxicology; Sodium Channels - metabolism; Vaccine; 心律失常; 电生理学; 钠离子通道
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2008.23

Aim： 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 （INa） 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 （40-120μmol/L） on the Na^＋ current in the two groups were then observed. Results： Tet （60-120 pmol/L） decreased INa 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 INa was shifted to more negative voltages in the two groups. Tet delayed the time-dependent recovery of INa in a concentration dependent manner in both AF and SR cells; however, there were no differences in the effects of Tet on INa density and properties in the two groups. The INa density of AF patients did not differ from that of the SR patients. Conclusion： 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.