[논문]Differential effects of ginsenoside metabolites on slowly activating delayed rectifier K+ and KCNQ1 K+ channel currents

Choi, Sun-Hye; Lee, Byung-Hwan; Kim, Hyeon-Joong; Jung, Seok-Won; Hwang, Sung-Hee; Nah, Seung-Yeol

doi:10.5142/jgr.2013.37.324

Differential effects of ginsenoside metabolites on slowly activating delayed rectifier K+ and KCNQ1 K+ channel currents 원문보기

Journal of ginseng research = 高麗人參學會誌, v.37 no.3, 2013년, pp.324 - 331

Choi, Sun-Hye (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio) , Lee, Byung-Hwan (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio) , Kim, Hyeon-Joong (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio) , Jung, Seok-Won (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio) , Hwang, Sung-Hee (Department of Pharmaceutical Engineering, Sangji University) , Nah, Seung-Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio)

Abstract ▼ AI-Helper

Channels formed by the co-assembly of the KCNQ1 subunit and the mink (KCNE1) subunit underline the slowly activating delayed rectifier $K^+$ channels ($I_{Ks}$) 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 $K^+$ ($I_{Ks}$) channels. In the present study, we examined the effect of protopanaxatriol (PPT) and compound K (CK) on KCNQ1 $K^+$ and $I_{Ks}$ channel activity expressed in Xenopus oocytes. PPT more strongly inhibited the $I_{Ks}$ channel currents than the currents of KCNQ1 $K^+$ alone in concentration- and voltage-dependent manners. The $IC_{50}$ values on $I_{Ks}$ and KCNQ1 alone currents for PPT were $5.18{\pm}0.13$ and $10.04{\pm}0.17{\mu}M$, respectively. PPT caused a leftward shift in the activation curve of $I_{Ks}$ channel activity, but minimally affected KCNQ1 alone. CK exhibited slight inhibition on $I_{Ks}$ and KCNQ1 alone $K^+$ channel currents. These results indicate that ginsenoside metabolites show limited effects on $I_{Ks}$ channel activity, depending on the structure of the ginsenoside metabolites.

주제어

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제안 방법

The current–voltage relationship was examined, and the current responses evoked by voltage steps (i.e., a series of voltage pulses of 3-s duration given in 10-mV increments and 10-s intervals with a holding potential of –80 mV) were used to construct the I-V curve.
The oocytes were impaled with 2 microelectrodes filled with 3M KCl (0.2 to 0.7 MΩ), and electrophysiological experiments were carried out at room temperature by using an Oocyte Clamp (OC-725C; Warner Instruments, Hamsden, CT, USA).

대상 데이터

Ginsenoside metabolites, such as CK and PPT, were provided by the AMBO Institute (Seoul, Korea) (Fig. 1). The cDNAs for human KCNQ channels (Gene Bank ID.
X. laevis frogs were purchased from Xenopus I (Ann Arbor, MI, USA). Their care and handling procedures were performed in accordance with the institutional guidelines of Konkuk University.

데이터처리

The significance of differences between the mean control and treatment values was determined using Student’s t-test.

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