title: Differential effects of ginsenoside metabolites on HERG k channel currents.
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 Rg3 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 α subunits in Xenopus oocytes. CK induced a large persistent deactivating-tail current (Ideactivating-tail ) and significantly decelerated deactivating current decay in a concentration-dependent manner. The EC50 for persistent Ideactivating-tail was 16.6±1.3 μM. In contrast to CK, PPT accelerated deactivating-tail current deactivation. PPD itself had no effects on deactivating-tail currents, whereas PPD inhibited ginsenoside Rg3-induced persistent Ideactivating-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.
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Shin
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Kang
authors.forename: Hyeon-Joong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Oh
authors.forename: Chun Sik
authors.initials: CS
authors.lastname: Bae
authors.forename: Soo-Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
keywords: Ginsenoside metabolites; Human ether-a-go-go-related gene K+ channel; Human heart; Panax ginseng