Ginsenoside Re increases human coronary artery endothelial SK(Ca) current and nitric oxide release via glucocorticoid receptor-PI3K-Akt/PKB pathway.

BACKGROUND: Ginsenoside Re (Re) has been shown to activate small-conductance calcium-activated potassium (SK(Ca)) current in human coronary artery endothelial cells (HCAECs). We aimed to investigate whether Re increased SK(Ca) current via glucocorticoid receptor (GR), its non-genomic pathway phosphoinositide 3-kinase-protein kinase B (PI3K-Akt/PKB), and endothelial nitric oxide synthase (eNOS), and whether SK(Ca) mediated Re-induced increase in nitric oxide (NO), prostacyclin (PGI(2)), epoxyeicosatrienoic acid (EET), and/or hydrogen peroxide (H(2)O(2)). METHODS: Whole-cell patch clamp technique was employed to study Re-activated HCAEC currents, using specific inhibitors of the proposed mediating pathway. NO and H(2)O(2) were assayed with colorimetric methods; PGI(2) and EET were investigated using ELISA. eNOS phosphorylation was assessed using Western blot analysis. RESULTS: Re (1 μM) significantly increased HCAEC whole-cell current at +80 mV to 173.73 ± 43.90 % (mean ± SD). Apamin (SK(Ca) blocker) could virtually eliminate Re-induced current and apamin-insensitive current could not be increased by Re, while blockers of other endothelial potassium channels did not produce the same effects. Moreover, antagonists of GR, PI3K, Akt/PKB, and eNOS effectively prevented Re's action. Re-induced eNOS phosphorylation and NO production could be prevented by blockers of SK(Ca), GR, or Akt/PKB, but Re-induced PGI(2) production could not be prevented by apamin, while EET and H(2)O(2) were not increased by Re. CONCLUSION: Re enhances SK(Ca) current and NO production via GR-PI3K-Akt/PKB and eNOS activation; in turn, SK(Ca) current is essential for Re-increased NO. However, Re-induced PGI(2) release is independent of SK(Ca) current. These findings could facilitate further research about ginseng effects on coronary artery and possible use in cardiovascular diseases.