Effects of ginsenosides and their metabolites on voltagedependent Ca<SUP>2+</SUP> channel subtypes

초록

In previous reports we demonstrated that ginsenosides, active ingredients of Panax ginseng, affect some subsets of voltage-dependent Ca2+ channels in neuronal cells expressed in Xenopus laevis oocytes. However, the major component(s) of ginseng that affect cloned Ca2+ channel subtypes such as alpha(1C) (L)-, alpha(1B) (N)-, alpha(1A) (P/Q)-, alpha(1E) (R)- and alpha(1G) (T) have not been identified. Here, we used the two-microelectrode voltage clamp technique to characterize the effects of ginsenosides and ginsenoside metabolites on Ba2+ currents (I-Ba) in Xenopus oocytes expressing five different Ca2+ 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 otic-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 alpha(1C)- and alpha(1E)-type Ca2+ channels. Compound K (CK), a protopanaxadiol ginsenoside metabolite, strongly inhibited only the alpha(1G)-type of Ca2+ 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 Ca2+ channels in Panax ginseng, and that they show some Ca2+ channel selectivity.

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