Characteristics of ginsenoside Rg(3)-mediated brain Na+ current inhibition
DC Field | Value | Language |
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dc.contributor.author | Lee, Jun-Ho | - |
dc.contributor.author | Jeong, Sang Min | - |
dc.contributor.author | Kim, Jong-Hoon | - |
dc.contributor.author | Lee, Byung-Hwan | - |
dc.contributor.author | Yoon, In-Soo | - |
dc.contributor.author | Lee, Joon-Hee | - |
dc.contributor.author | Choi, Sun-Hye | - |
dc.contributor.author | Kim, Dong-Hyun | - |
dc.contributor.author | Rhim, Hyewhon | - |
dc.contributor.author | Kim, Sung Soo | - |
dc.contributor.author | Kim, Jai-Il | - |
dc.contributor.author | Jang, Choon-Gon | - |
dc.contributor.author | Song, Jin-Ho | - |
dc.contributor.author | Nah, Seung-Yeol | - |
dc.date.available | 2019-05-30T07:36:09Z | - |
dc.date.issued | 2005-10 | - |
dc.identifier.issn | 0026-895X | - |
dc.identifier.issn | 1521-0111 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24505 | - |
dc.description.abstract | We demonstrated previously that ginsenoside Rg(3) (Rg(3)), an active ingredient of Panax ginseng, inhibits brain-type Na+ channel activity. In this study, we sought to elucidate the molecular mechanisms underlying Rg(3)-induced Na+ channel inhibition. We used the two-microelectrode voltage-clamp technique to investigate the effect of Rg(3) on Na+ currents (I-Na) in Xenopus laevis oocytes expressing wild-type rat brain Na-V 1.2 alpha and beta 1 subunits, or mutants in the channel entrance, the pore region, the lidocaine/tetrodotoxin (TTX) binding sites, the S4 voltage sensor segments of domains I to IV, and the Ile-Phe-Met inactivation cluster. In oocytes expressing wild-type Na+ channels, Rg(3) induced tonic and use-dependent inhibitions of peak I-Na. The Rg(3)- induced tonic inhibition of I-Na was voltage-dependent, dose-dependent, and reversible, with an IC50 value of 32 +/- 6 mu M. Rg(3) treatment produced a 11.2 +/- 3.5 mV depolarizing shift in the activation voltage but did not alter the steady-state inactivation voltage. Mutations in the channel entrance, pore region, lidocaine/TTX binding sites, or voltage sensor segments did not affect Rg(3)-induced tonic blockade of peak I-Na. However, Rg(3) treatment inhibited the peak and plateau I-Na in the IFMQ3 mutant, indicating that Rg(3) inhibits both the resting and open states of Na+ channel. Neutralization of the positive charge at position 859 of voltage sensor segment domain II abolished the Rg(3)-induced activation voltage shift and use-dependent inhibition. These results reveal that Rg(3) is a novel Na+ channel inhibitor capable of acting on the resting and open states of Na+ channel via interactions with the S4 voltage-sensor segment of domain II. | - |
dc.format.extent | 13 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS | - |
dc.title | Characteristics of ginsenoside Rg(3)-mediated brain Na+ current inhibition | - |
dc.type | Article | - |
dc.identifier.doi | 10.1124/mol.105.015115 | - |
dc.identifier.bibliographicCitation | MOLECULAR PHARMACOLOGY, v.68, no.4, pp 1114 - 1126 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000232002500022 | - |
dc.identifier.scopusid | 2-s2.0-25144469808 | - |
dc.citation.endPage | 1126 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 1114 | - |
dc.citation.title | MOLECULAR PHARMACOLOGY | - |
dc.citation.volume | 68 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordPlus | ADRENAL CHROMAFFIN CELLS | - |
dc.subject.keywordPlus | NICOTINIC ACETYLCHOLINE-RECEPTORS | - |
dc.subject.keywordPlus | RAT HIPPOCAMPAL-NEURONS | - |
dc.subject.keywordPlus | I ANTIARRHYTHMIC AGENT | - |
dc.subject.keywordPlus | STATE-DEPENDENT BLOCK | - |
dc.subject.keywordPlus | SODIUM CHANNEL-II | - |
dc.subject.keywordPlus | XENOPUS OOCYTES | - |
dc.subject.keywordPlus | CATECHOLAMINE SECRETION | - |
dc.subject.keywordPlus | MOLECULAR DETERMINANTS | - |
dc.subject.keywordPlus | LOCAL-ANESTHETICS | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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