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 IHERG 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 IHERG, while ALL (30 μmol/L) did not affect the steady-state inactivation of IHERG. Furthermore, BTHP, but not ALL, shortened the time constants of fast inactivation and slow time constants of deactivation of IHERG. But both the drugs markedly lengthened the time constants for recovery of IHERG 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.
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Acknowledgements
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.
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Lin, K., Liu, Yq., Xu, B. et al. Allocryptopine and benzyltetrahydropalmatine block hERG potassium channels expressed in HEK293 cells. Acta Pharmacol Sin 34, 847–858 (2013). https://doi.org/10.1038/aps.2012.176
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DOI: https://doi.org/10.1038/aps.2012.176
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