Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Differential Effects of Ginsenoside Metabolites on HERG K+ Channel Currents

  • Choi, Sun-Hye (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Shin, Tae-Joon (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Hwang, Sung-Hee (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Lee, Byung-Hwan (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Kang, Ji-Yeon (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Hyeon-Joong (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Oh, Jae-Wook (College of Food Science and Biotechnology of Animal Resources, Konkuk University) ;
  • Bae, Chun-Sik (College of Veterinary Medicine, Animal Medical Institute, Chonnam National University) ;
  • Lee, Soo-Han (Department of Clinical Pharmacology and Therapeutics, University of Ulsan College of Medicine) ;
  • Nah, Seung-Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
  • Received : 2010.12.28
  • Accepted : 2011.02.09
  • Published : 2011.06.29
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Abstract

The human ether-a-go-go-related gene (HERG) cardiac $K^+$ channels are one of the representative pharmacological targets for development of drugs against cardiovascular diseases such as arrhythmia. Panax ginseng has been known to exhibit cardioprotective effects. In a previous report we demonstrated that ginsenoside $Rg_3$ regulates HERG $K^+$ channels by decelerating deactivation. However, little is known about how ginsenoside metabolites regulate HERG $K^+$ channel activity. In the present study, we examined the effects of ginsenoside metabolites such as compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) on HERG $K^+$ channel activity by expressing human a subunits in Xenopus oocytes. CK induced a large persistent deactivatingtail current ($I_{deactivating-tail}$) and significantly decelerated deactivating current decay in a concentration-dependent manner. The $EC_{50}$ for persistent $I_{deactivating-tail}$ was $16.6{\pm}1.3$ ${\mu}M$. In contrast to CK, PPT accelerated deactivating-tail current deactivation. PPD itself had no effects on deactivating-tail currents, whereas PPD inhibited ginsenoside $Rg_3$-induced persistent $I_{deactivating-tail}$ and accelerated HERG $K^+$ channel deactivation in a concentration-dependent manner. These results indicate that ginsenoside metabolites exhibit differential regulation on Ideactivating-tail of HERG $K^+$ channel.

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References

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