Effects of ginsenosides and their metabolites on voltage-dependent Ca(2+) channel subtypes.
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.
Lee
Jun-Ho
JH
Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
Jeong
Sang Min
SM
Kim
Jong-Hoon
JH
Lee
Byung-Hwan
BH
Yoon
In-Soo
IS
Lee
Joon-Hee
JH
Choi
Sun-Hye
SH
Lee
Sang-Mok
SM
Park
Yong-Sun
YS
Lee
Jung-Ha
JH
Kim
Sung Soo
SS
Kim
Hyoung-Chun
HC
Lee
Boo-Yong
BY
Nah
Seung-Yeol
SY
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
D015220:Calcium Channels; D036145:Ginsenosides