A hallmark of coronary heart disease (CHD) is impaired coronary vasodilation. Bilobalide, a main constituent of the terpenoids found in Ginkgo biloba leaves, has been found to induce vasorelaxation in some vascular beds. However, little information exists about bilobalide effects on endothelial cells and the involved mechanisms, and there has been no bilobalide study on human coronary artery endothelial cells (HCAECs). To better understand the electrophysiological profile of bilobalide effects in human coronary artery, we aimed to elucidate the effects of bilobalide on K+ currents in HCAECs. Standard whole-cell voltage-clamp technique was employed to record HCAEC ionic currents elicited from a holding potential of -40 mV to voltage steps (-100 to +80 mV; 20 mV increments) for 600 ms. Bilobalide powder was dissolved in DMSO (maximum 0.33 %, v/v) which did not alter HCACE currents. Currents in 1 to 100 µM bilobalide were compared to control. Values are mean ± SEM. Bilobalide, at 10, 30 and 100 µM, dose-dependently and reversibly increased HCAEC currents; mean current density at +60 mV was enhanced by 33.2 ± 7.5% (n=6), 42.4 ± 5.0% (n=6) and 47.3 ± 6.7% (n=5), respectively, when compared with controls (p<0.01; ANOVA with post hoc Dunnett’s test). The EC50 and maximum increase, obtained from a non-linear fit of the data to the dose-response equation, were 6.71 ± 1.28 µM and 45.5 ± 4.4 %. The effect of bilobalide on small-, intermediate- and large-conductance calcium-activated potassium channels (SKCa, IKCa and BKCa channel, respectively), were investigated using specific blockers: 0.5 µM apamin, 10 µM clotrimazole and 1 mM TEA, respectively. Bilobalide-induced HCAEC currents were significantly reduced when exposed to apamin and TEA by 23.3 ± 2.2 % (n=6) and 18.7 ± 4.6 % (n=6, p<0.01; t-test), but no significant alteration was observed in clotrimazole, suggesting that bilobalide may increase HCAEC currents via SKCa and BKCa , but not IKCa channels. In addition, exposure of bilobalide-induced HCAEC currents to 10 µM La3+, a specific blocker of nonselective cation (NSC) channel, yielded no statistical difference from control currents. Evidently, NSC channel may not be involved in bilobalide-enhanced HCAEC current. Bilobalide increases HCAEC currents dose-dependently through SKCa and BKCa channels. These finding may provide a basis for the mechanism of bilobalide-induced vasodilator release, involving endothelial ion channels, and suggest that bilobalide may be therapeutically effective in cardiovascular disease.