Effects of an extract of Ginkgo biloba On the action potential and associated transmembrane ionic currents in mammalian cardiac myocytes: Inhibition of isoproterenol-induced chloride current

Ventricular myocytes of guinea pig heart were used to examine the effects of an extract of Ginkgo biolba (EGb 761) on the action potential and individual transmembrane ionic currents. Elecrophysiological events were recorded using the “whole-cell” configuration of the patch-clamp technique. A systematic analysis of the data revealed that EGb 761 (5-50 μg/ml) did not affect the normal action potential or the various ionic currents involved in its generation; i.e., fast inward sodium current (I_Na), inward calcium currents (I_CaT and I_CaL), delayed outward potassium current (I_K), inward rectifying potassium current (I_K1), and ATP-senstive potassium current (I_K-ATP) evoked by 2,4-dinitrophenol (2,4-DNP). However, EGb 761 (≥5 μg/ml) elicited a pronouced concentration-dependent and reversible inhibiton of isoproternol-induced Cl^? current (I_Cl), the maximal effect being observed at 50 μg/ml. This current may be significantly involved in sympathetic hyperactivity, hypoxia, and ischemia, pathophysiological conditions for which EGb 761 offers therapeutic benefit. The basic mechanism(s) underlying the inhibitory effect of EGb 761 on I_Cl and the constituent(s) of EGb 761 responsible for this action remain to be identified, but it seems clear, from results which showed that neither ginkgolide B (50–500 ng/ml) nor biolobalide (150–1,500 ng/ml) influenced this current, that a terpenoid constituent of EGb 761 is probably not involved.