Ginsenoside Re enhances small-conductance Ca2 +-activated K+ current in human coronary artery endothelial cells

Abstract

© 2014 Elsevier Inc. All rights reserved. Main methods: Ionic currents of cultured HCAECs were studied using whole-cell patch clamp technique. Aims: 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 Ca2+-activated K+(KCa) channels. The objectives of this study, therefore, were to test 1) whether vasorelaxing ginsenoside Re could affect KCacurrent, 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.Key findings: Ginsenoside Re dose-dependently increased endothelial outward currents, with an EC50of 408.90±1.59 nM, and a maximumincrease of 36.20± 5.62% (mean±SEM; p <0.05). Apamin, an SKCachannel inhibitor, could block this effect, while La3+, a nonselective cation channel (NSC) blocker, could not.When NSC channel, inward-rectifier K+channel, intermediate-, and large-conductance KCachannels were simultaneously blocked, ginsenoside Re could still increase outward currents significantly (35.49± 4.22%; p b 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 SKCachannel activation, and NSC channel was not involved.Significance: This is the first report to demonstrate that ginsenoside Re could increase SKCachannel activity in HCAECs. This can be a mechanism mediating ginseng's beneficial actions on coronary vessels.