Antiarrhythmic ionic mechanism of Guanfu base A-Selective inhibition of late sodium current in isolated ventricular myocytes from guinea pigs

The present study was designed to determine the effects of Guanfu base A (GFA) on the late sodium current (INa.L), transient sodium current (INa.T), HERG current (IHERG), and Kv1.5 current (IKv1.5).The values of INa.L, INa.T, IHERG and IKv1.5 were recorded using the whole-cell patch clamp technique. Compared with other channels, GFA showed selective blocking activity in late sodium channel. It inhibited INa.L in a concentration-dependent manner with an IC50 of (1.570.14) molL-1, which was significantly lower than its IC50 values of (21.174.51) molL-1 for the INa.T. The inhibitory effect of GFA on INa,L was not affected by 200 molL-1 H2O2. It inhibited IHERG with an IC50 of (27334) molL-1 and has slight blocking effect on IKv1.5, decreasing IKv1.5 by only 20.6% at 200 molL-1. In summary,GFA inhibited INa.L selectively and remained similar inhibition in presence of reactive oxygen species.. These findings may suggest a novel molecular mechanism for the potential clinical application of GFA in the treatment of cardiovascular disorders.