Ginkgo biloba extract and ginkgolide antiarrhythmic potential by targeting hERG and ICa-L channel

We investigated the effects of ginkgo biloba extract (gbe) and ginkgolide (gld) on human ether-a-go-go-related gene (herg)-encoded k+ channels and its underlying mechanisms in the herg-hek293 cell line by determining gbe- and gld-induced changes in action potential duration (apd),l-type calcium currents (ica-l),and the intracellular calcium concentration ([ca2+]i) in guinea-pig ventricular myocytes. herg currents,apd and ica-l were recorded using the whole-cell patch clamp technique,the [ca2+]i was examined by an immunofluorescence experiment. in the present study,we found that a low concentration of gbe (0.005 mg/ml) increased herg currents,but the high concentration of gbe (from 0.05 to 0.25 mg/ml) reduced herg currents. gld reduced herg currents in a concentration-dependent manner (from 0.005 to 0.25 mg/ml). both gbe and gld altered kinetics of the herg channel. gbe accelerated the activation of herg channels without changing the inactivation curve,but reduced the time constant of inactivation; gld did not shift the activation or the inactivation curve,but only reduced the time constant of inactivation. both gbe and gld shortened the apd,inhibited the ica-l currents,and decreased the [ca2+]i in isolated guinea-pig ventricular myocytes. the results indicate that gbe and gld can prevent ischemic arrhythmias and have an antiarrhythmic effect potential via inhibition of ikr and ica-l currents. © the japanese pharmacological society.