Ginsenoside Rg3 activates human KCNQ1 K+ channel currents through interacting with the K318 and V319 residues: A role of KCNE1 subunit

Choi, Sun-Hye; Shin, Tae‐Joon; Lee, Byung-Hwan; Chu, Daehyun; Choe, Han; Pyo, Mi-Kyung; Hwang, Sung‐Hee; Kim, Bora; Lee, Sang-Mok; Lee, Jun-Ho; Kim, Dong‐Hyun; Kim, Hyoung‐Chun; Rhim, Hyewhon; Nah, Seung-Yeol

doi:10.1016/j.ejphar.2010.04.001

Cited by 22 publications

(28 citation statements)

References 23 publications

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“…In a previous study, we demonstrated that ginsenoside Rg 3 , a ginseng saponin, also enhances I Ks channel currents following depolarization (Choi et al, 2010). We found that gintonin differs from ginsenoside Rg 3 in the regulatory patterns for I Ks channel activation.…”

Section: Resultsmentioning

confidence: 97%

“…Thus, ginsenoside Rg 3 -induced I Ks current enhancement does not act via a membrane receptor signaling transduction pathway. Instead, ginsenoside Rg 3 -induced enhancement of I Ks channels currents was abolished by substitution of the K318 and V319 residues located at the channel pore entrance (Choi et al, 2010). Thus, ginsenoside Rg 3 regulates I Ks activity through direct interaction with channel proteins at the channel pore entrance.…”

Section: Resultsmentioning

confidence: 99%

“…6). The EC 50 of gintonin is approximately 35nM (under the assumption that the molecular weight of gintonin is 20 kDa) (Hwang et al, 2012), whereas that of the ginsenoside Rg 3 was about 15 μM for I Ks activation (Choi et al, 2010). In addition, interruption of the receptor signaling pathway by inhibitors or mutations abolished or attenuated gintonin-mediated but not ginsenoside Rg 3- mediated I Ks channel activation (data not shown).…”

Section: Resultsmentioning

confidence: 99%

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Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites

Choi¹,

Lee²,

Kim³

et al. 2014

Molecules and Cells

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Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca2+]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K+ (IKs) channel is a cardiac K+ channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating IKs channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human IKs channel activity by expressing human IKs channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the IKs channel was 0.05 ± 0.01 μg/ml. Gintonin-mediated activation of the IKs channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the IKs channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca2+]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on IKs channel. However, gintonin had no effect on hERG K+ channel activity. These results show that gintonin-mediated enhancement of IKs channel currents is achieved through binding of the [Ca2+]i/CaM complex to the C terminus of KCNQ1 subunit.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites

Choi¹,

Lee²,

Kim³

et al. 2014

Molecules and Cells

Self Cite

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“…Also Rg3-activated human KCNQ1 K' channel currents through interacting with the K318 and V319 residues (Choi et al 2010). Alpha7 nicotinic acetylcholine receptor was regulated by ginsenoside through a role for Leu247 residue within transmembrane domain 2 ) and human Kv1.4 channel currents were regulated by Rg3 without the N-terminal rapid inactivation ).…”

Section: Discussionmentioning

confidence: 99%

The role of ginseng total saponin in transient receptor potential melastatin type 7 channels

Kim

2012

Animal Cells and Systems

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Although ginsenosides have a variety of physiologic or pharmacologic functions in various regions, there are only a few reports on the effects of transient receptor potential melastatin 7 (TRPM7) channels. Here, we showed evidence suggesting that TRPM7 channels play an important role in ginseng total saponin (GTS)-mediated cellular injury. The combination techniques of electrophysiology, pharmacological analysis, small interfering RNA (siRNA) method and cell death assays were used. GTS depolarized the resting membrane potentials and decreased the amplitude of pacemaker potentials in cultured interstitial cells of Cajal (ICCs) in gastrointestinal (GI) tract. The TRPM7-like currents in single ICCs and the overexpressing TRPM7 in HEK293 cells were inhibited by GTS. However, GTS had no effect on Ca 2 ' -activated Cl ( conductance. GTS inhibited the survival of human gastric (AGS) and breast (MCF-7) adenocarcinoma cells. Also, GTS inhibited the TRPM7-like currents in AGS and MCF-7 cells. The GTSmediated cytotoxicity was inhibited by TRPM7-specific siRNA. In addition, we showed that overexpression of TRPM7 channels in HEK293 cells was inhibited by GTS. Thus, TRPM7 channels are involved in GTS-mediated cell death in AGS and MCF-7 cells, and these channels may represent a novel target for physiological disorders where GTS plays an important role.

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“…Ginsenosides have been shown to interact with a variety of ion channels, including the GABA A receptor (Rg3) [145], KCNQ1 K + channels (Rg3) [146], Na + channels (Rg3) [147], and L-type, N-type, P/Q-type, and T-type Ca 2+ channels [148]. The lignan magnolol from Magnolia officinalis was reported to increase the probability of BK Ca channel openings in a concentration-dependent manner with an EC 50 value of 1.5 μM [149].…”

Section: Other Ion Channelsmentioning

confidence: 99%

A pharmacological basis of herbal medicines for epilepsy

Sucher¹,

Carles²

2015

Epilepsy & Behavior

116

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Ginsenoside Rg3 activates human KCNQ1 K+ channel currents through interacting with the K318 and V319 residues: A role of KCNE1 subunit

Cited by 22 publications

References 23 publications

Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites

Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites

The role of ginseng total saponin in transient receptor potential melastatin type 7 channels

A pharmacological basis of herbal medicines for epilepsy

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