Allocryptopine and benzyltetrahydropalmatine block hERG potassium channels expressed in HEK293 cells

Abstract

Aim:Allocryptopine (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 IHERG 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 IC 50 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. © 2013 CPS and SIMM.