title: Effects of ginsenosides and their metabolites on voltage-dependent Ca(2+) channel subtypes.
abstract: In previous reports we demonstrated that ginsenosides, active ingredients of Panax ginseng, affect some subsets of voltage-dependent Ca(2+) channels in neuronal cells expressed in Xenopus laevis oocytes. However, the major component(s) of ginseng that affect cloned Ca(2+) channel subtypes such as alpha(1C) (L)-, alpha(1B) (N)-, alpha(1A) (P/Q)-, a1E (R)- and a1G (T) have not been identified. Here, we used the two-microelectrode volt-age clamp technique to characterize the effects of ginsenosides and ginsenoside metabolites on Ba(2+) currents (IBa) in Xenopus oocytes expressing five different Ca(2+) channel subtypes. Exposure to ginseng total saponins (GTS) induced voltage-dependent, dose-dependent and reversible inhibition of the five channel subtypes, with particularly strong inhibition of the a1G-type. Of the various ginsenosides, Rb(1), Rc, Re, Rf, Rg(1), Rg(3), and Rh(2), ginsenoside Rg(3) also inhibited all five channel subtypes and ginsenoside Rh(2) had most effect on the a1C- and a1E-type Ca(2+) channels. Compound K (CK), a protopanaxadiol ginsenoside metabolite, strongly inhibited only the a(1G)-type of Ca(2+) channel, whereas M4, a protopanaxatriol ginsenoside metabolite, had almost no effect on any of the channels. Rg(3), Rh(2), and CK shifted the steady-state activation curves but not the inactivation curves in the depolarizing direction in the alpha(1B)- and alpha(1A)-types. These results reveal that Rg(3), Rh(2) and CK are the major inhibitors of Ca(2+) channels in Panax ginseng, and that they show some Ca(2+) channel selectivity.
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: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Jeong
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Yoon
authors.forename: Joon-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Sang-Mok
authors.initials: SM
authors.lastname: Lee
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Park
authors.forename: Jung-Ha
authors.initials: JH
authors.lastname: Lee
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Boo-Yong
authors.initials: BY
authors.lastname: Lee
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D036145:Ginsenosides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D014981:Xenopus
chemical_list: D015220:Calcium Channels; D036145:Ginsenosides