Inhibition of sibutramine on hERG potassium current / 西安交通大学学报(医学版)

ABSTRACT

Objective To study the effects of sibutramine on the human-ether-a-go-go-related gene (hERG) current in HEK293 cell line that overexpresses hERG potassium channels. Methods HEK293 cell line that overexpresses hERG potassium channels was constructed. Whole cell patch clamp techniques were employed to investigate the effects of sibutratime on Iherg in the cell line. Results Sibutramine reduced hERG current in a concentration-dependent mannerthe inhibition rate was (8.82?2.32)%,(26.7?5.78)%,(44.93?4.60)% and (85.22?3.37)% at the dose of 3,10,30 and 100 ?mol/L. IC50 value was 32.66 ?mol/L (n=8). Ⅰ-Ⅴ relationship was inhibited by sibutramine (3,10,30 and 100 ?mol/L) at membrane potentials from -10 mV to +60 mV (step) and from 0 mV to +60 mV (tail) (n=8). Conclusion Sibutramine significantly inhibited Iherg in HEK293 cell line that overexpresses hERG potassium channels in a concentration-dependent manner,which may be a major mechanism of causing QT interval prolongation.