AIIocryptopine and benzyltetrahydropalmatine block hERG potassium channels expressed in HEK293 cells  

作　　者：Kun LIN Yu-qi LIU Bin XU Jin-liao GAO Yi-cheng FU Yu CHEN Qiao XUE Li YANG 

机构地区：[1]Institute of Geriatric Cardiology, the General Hospital of People's Liberation Army, Beijing 100853, China

出　　处：《Acta Pharmacologica Sinica》2013年第6期847-858,共12页中国药理学报（英文版）

基　　金：This study was supported by grants from the National Natural Science Foundation of China （No 81170177, No 30770901）. The authors would like to thank Prof Silvia G PRIORI from Molecular Cardiology, Fondazione Salvatore Maugeri IRCCS, at the University of Pavia in Italy for generously providing the hERG plasmid.

摘　　要：Aim： AIIocryptopine （ALL） is an alkaloid extracted from Corydalis decumbens （Thunb） Pers. Papaveraceae, whereas benzyltetrahydropalmatine （BTHP） is a derivative of tetrahydropalmatine extracted from Corydalis ambigua （Pall） Cham et Schlecht. The aim of this study was to investigate the effects of ALL and BTHP on the human ether-a-go-go related gene （hERG） current expressed in HEK293 cells. Methods： Cultured HEK293 cells were transiently transfected with hERG channel cDNA plasmid pcDNA3.1 using Lipofectamine. The whole-cell current I_HERG was evoked and recorded using Axon MultiClamp 700B amplifier. The drugs were applied via supserfusion. Results： Both ALL and BTHP reversibly suppressed the amplitude and density of I_HERG in concentration- and voltage-dependent manners （the respective IC50 value was 49.65 and 22.38 μmol/L）. BTHP （30 μmol/L） caused a significant negative shift of the steady-state inactivation curve of I_HERG, while ALL （30 μmol/L） did not affect the steady-state inactivation of I_HERG. Furthermore, BTHP, but not ALL, shortened the time constants of fast inactivation and slow time constants of deactivation of I_HERG. But both the drugs markedly lengthened the time constants for recovery of I_HERG from inactivation. Using action potential waveform pulses, it was found that both the drugs at 30 μmol/L significantly suppressed the current densities in the late phase of action potential, but did not significantly affect the current densities in the early phase of action potential. Conclusion： Both ALL and BTHP derived from Chinese herbs potently block hERG current.Aim： AIIocryptopine （ALL） is an alkaloid extracted from Corydalis decumbens （Thunb） Pers. Papaveraceae, whereas benzyltetrahydropalmatine （BTHP） is a derivative of tetrahydropalmatine extracted from Corydalis ambigua （Pall） Cham et Schlecht. The aim of this study was to investigate the effects of ALL and BTHP on the human ether-a-go-go related gene （hERG） current expressed in HEK293 cells. Methods： Cultured HEK293 cells were transiently transfected with hERG channel cDNA plasmid pcDNA3.1 using Lipofectamine. The whole-cell current I_HERG was evoked and recorded using Axon MultiClamp 700B amplifier. The drugs were applied via supserfusion. Results： Both ALL and BTHP reversibly suppressed the amplitude and density of I_HERG in concentration- and voltage-dependent manners （the respective IC50 value was 49.65 and 22.38 μmol/L）. BTHP （30 μmol/L） caused a significant negative shift of the steady-state inactivation curve of I_HERG, while ALL （30 μmol/L） did not affect the steady-state inactivation of I_HERG. Furthermore, BTHP, but not ALL, shortened the time constants of fast inactivation and slow time constants of deactivation of I_HERG. But both the drugs markedly lengthened the time constants for recovery of I_HERG from inactivation. Using action potential waveform pulses, it was found that both the drugs at 30 μmol/L significantly suppressed the current densities in the late phase of action potential, but did not significantly affect the current densities in the early phase of action potential. Conclusion： Both ALL and BTHP derived from Chinese herbs potently block hERG current.

关 键 词：allocryptopine benzyltetrahydropalmatine hERG current whole-cell patch-clamp recording anti-arrhythmic agent 

分 类 号：Q813.11[生物学—生物工程] Q73