title: Ginsenoside Re enhances small-conductance Ca(2+)-activated K(+) current in human coronary artery endothelial cells.
abstract: OBJECTIVE
  Ginsenosides, active components in ginseng, have been shown to increase nitric oxide (NO) production in aortic endothelial cells. This effect was reversed by tetraethylammonium (TEA) inhibition of endothelial Ca(2+)-activated K(+) (KCa) channels. The objectives of this study, therefore, were to test 1) whether vasorelaxing ginsenoside Re could affect KCa current, an important regulator of NO production, in human coronary artery endothelial cells (HCAECs); and 2) whether small-conductance KCa (SKCa) channel was the channel subtype involved.
  
  
  METHODS
  Ionic currents of cultured HCAECs were studied using whole-cell patch clamp technique.
  
  
  RESULTS
  Ginsenoside Re dose-dependently increased endothelial outward currents, with an EC50 of 408.90±1.59nM, and a maximum increase of 36.20±5.62% (mean±SEM; p<0.05). Apamin, an SKCa channel inhibitor, could block this effect, while La(3+), a nonselective cation channel (NSC) blocker, could not. When NSC channel, inward-rectifier K(+) channel, intermediate-, and large-conductance KCa channels were simultaneously blocked, ginsenoside Re could still increase outward currents significantly (35.49±4.22%; p<0.05); this effect was again abolished by apamin. Repeating the experiments when Cl(-) channel was additionally blocked gave similar results. Finally, we demonstrated that ginsenoside Re could hyperpolarize HCAECs; this effect was reversed by apamin. These data clearly indicate that ginsenoside Re increased HCAEC outward current via SKCa channel activation, and NSC channel was not involved.
  
  
  CONCLUSIONS
  This is the first report to demonstrate that ginsenoside Re could increase SKCa channel activity in HCAECs. This can be a mechanism mediating ginseng's beneficial actions on coronary vessels.
authors.affiliation: Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Suporn
authors.initials: S
authors.lastname: Sukrittanon
authors.affiliation: Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Electronic address: wattana.wat@mahidol.ac.th.
authors.forename: Wattana B
authors.initials: WB
authors.lastname: Watanapa
authors.affiliation: Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Katesirin
authors.initials: K
authors.lastname: Ruamyod
mesh_terms: D001030:Apamin / Q000494:pharmacology; D002460:Cell Line; D003331:Coronary Vessels / Q000166:cytology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D007811:Lanthanum / Q000494:pharmacology; D005894:Panax / Q000737:chemistry; D018408:Patch-Clamp Techniques; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D036145:Ginsenosides; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014665:Vasodilator Agents; D001030:Apamin; C049864:ginsenoside Re; D007811:Lanthanum
keywords: Apamin; Ginseng; Ion channel; Whole-cell patch clamp technique