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 （1.57 ± 0.14） μmol＇L-1, which was significantly lower than its ICs0 values of （21.17 ± 4.51） μmol·L^-1 for the INa.X. The inhibitory effect of GFA on INa.L was not affected by 200 μmol·L^-1 H2O2. It inhibited InER6 with an ICs0 of （273± 34） μmol·L^-1 and has slight blocking effect on IKv1.5, decreasing IKv1.5 by only 20.6% at 200 μmol·L^-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.