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.