Channels formed by the co-assembly of the KCNQ1 subunit and the mink (KCNE1) subunit underline the slowly activating delayed rectifier K(+) channels (IKs ) in the heart. This K(+) channel is one of the main pharmacological targets for the development of drugs against cardiovascular disease. Panax ginseng has been shown to exhibit beneficial cardiovascular effects. In a previous study, we showed that ginsenoside Rg3 activates human KCNQ1 K(+) channel currents through interactions with the K318 and V319 residues. However, little is known about the effects of ginsenoside metabolites on KCNQ1 K(+) alone or the KCNQ1 + KCNE1 K(+) (IKs ) channels. In the present study, we examined the effect of protopanaxatriol (PPT) and compound K (CK) on KCNQ1 K(+) and IKs channel activity expressed in Xenopus oocytes. PPT more strongly inhibited the IKs channel currents than the currents of KCNQ1 K(+) alone in concentration- and voltage-dependent manners. The IC50 values on IKs and KCNQ1 alone currents for PPT were 5.18±0.13 and 10.04±0.17 μM, respectively. PPT caused a leftward shift in the activation curve of IKs channel activity, but minimally affected KCNQ1 alone. CK exhibited slight inhibition on IKs and KCNQ1 alone K(+) channel currents. These results indicate that ginsenoside metabolites show limited effects on IKs channel activity, depending on the structure of the ginsenoside metabolites.
Keywords: Ginsenoside metabolites; Human heart; Panax ginseng; Slowly activating delayed rectifier K+ channels (IKs).