Suppression of pacemaker activity by Ginkgo biloba extract and its main constituent, bilobalide in rat sino-atrial nodal cells

Effects of Ginkgo biloba extract (GBE) and bilobalide (a main constituent) on the pacemaker activity and the underlying ionic currents in rat sino-atrial (SA) nodal cells were investigated using patch-clamp techniques. Both GBE and bilobalide depressed the pacemaker activity in a concentration-dependent manner. At both 0.03 mg/ml GBE and 0.3 μM bilobalide, a negative chronotropic effect was produced. Dysrhythmias often occurred. The L-type Ca2+ current (ICa) and the hyperpolarization-activated inward current (If) decreased by 69.7 ± 3.2% (n = 6, P < 0.001) and by 12.6 ± 2.1% (n = 7, P < 0.05) at 0.03 mg/ml GBE, and by 51.2 ± 3.3% (n = 6, P < 0.01) and by 19.8 ± 2.2 % (n = 6, P < 0.05) at 0.3 μM bilobalide, respectively. The delayed rectifier K+ current (IK) also decreased. The inhibition was 12.3 ± 2.0% (n = 6, P < 0.05) at 0.03 mg/ml GBE, and was 28.0 ± 2.9% (n = 6, P < 0.05) at 0.3 μM bilobalide. These results indicate that cardiac ionic channels contributing to the pacemaking are highly sensitive to GBE and bilobalide, which can sufficiently modify the spontaneous activity in rat SA nodal cells.