Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Department of Physiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Life Sci. 2014 Oct 12;115(1-2):15-21. doi: 10.1016/j.lfs.2014.09.007. Epub 2014 Sep 19.
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.
Ionic currents of cultured HCAECs were studied using whole-cell patch clamp technique.
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.
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.
人参中的活性成分人参皂苷已被证明可增加主动脉内皮细胞中一氧化氮（NO）的产生。这种作用被内皮细胞 Ca2+激活的 K+（KCa）通道的四乙铵（TEA）抑制所逆转。因此，本研究的目的是：1）测试血管舒张人参皂苷 Re 是否可以影响人冠状动脉内皮细胞（HCAEC）中重要的 NO 产生调节剂 KCa 电流；2）确定涉及的通道亚型。
使用全细胞膜片钳技术研究培养的 HCAEC 的离子电流。
人参皂苷 Re 呈浓度依赖性增加内皮细胞外向电流，EC50 为 408.90±1.59nM，最大增加 36.20±5.62%（平均值±SEM；p<0.05）。SKCa 通道抑制剂阿帕米可以阻断这种作用，而非选择性阳离子通道（NSC）阻滞剂 La3+则不能。当同时阻断 NSC 通道、内向整流钾（K+）通道、中电导和大电导 KCa 通道时，人参皂苷 Re 仍能显著增加外向电流（35.49±4.22%；p<0.05）；阿帕米再次消除了这种作用。当 Cl-通道被另外阻断时重复实验，得到了类似的结果。最后，我们证明人参皂苷 Re 可以使 HCAEC 超极化；阿帕米可逆转这种作用。这些数据清楚地表明，人参皂苷 Re 通过激活 SKCa 通道增加 HCAEC 的外向电流，而 NSC 通道不参与该过程。
这是首次报道人参皂苷 Re 可增加 HCAEC 中的 SKCa 通道活性。这可能是介导人参对冠状动脉有益作用的机制之一。
