Comparative Electropharmacological Actions of Some Constituents from Ginkgo biloba Extract in Guinea-pig Ventricular Cardiomyocytes

Effects of the constituents from Ginkgo biloba extract (GBE) on the action potentials and the ionic currents in guinea pig ventricular cardiomyocytes were investigated using whole-cell and current-clamp techniques. The constituents, ginkgolides A, B, C and quercetin, had depressant effects at 0.1-3muM on the action potential configuration. Ginkgolide A (1-3 muM) prolonged the action potential (action potential duration: APD) at 75% and 90% repolarizations (APD(75) and APD(90)). However, ginkgolides B and C at low concentrations prolonged APD, but at higher concentrations (>1 muM) shortened APD. Quercetin at 3 muM prolonged the APD, but not at the lower concentrations. These constituents also inhibited the V(max). The resting potential was unaffected. In voltage-clamp experiments, ginkgolides A and B (0.1-3 muM) markedly and concentration-dependently increased the Ca(2+) current (I(Ca)) and the delayed rectifier K(+) current (I(K)), and decreased the inwardly rectifying K(+) current (I(K1)). On the other hand, ginkgolide C failed to affect the I(Ca) but increased the I(K) by 14.0 +/- 2.3% (n = 6, P < 0.05) at 1 muM. Quercetin inhibited I(Ca), and enhanced I(K) but decreased I(K1). These responses to the constituents were almost reversible (80-90% of control) after a 10- to 20-min washout. These results indicate that even at acute administrations, these constituents produce the effective actions on the APD and the underlying ionic currents in cardiomyocytes. Each constituent does not exhibit a uniform response, although GBE acts as a net.