Differential Effects of Ginsenoside Metabolites on HERG K(+) Channel Currents

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 α subunits in Xenopus oocytes. CK induced a large persistent deactivating-tail 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±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 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 I(deactivating-tail) of HERG K(+) channel.