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

Abstract The present study was designed to determine the effects of Guanfu base A (GFA) on the late sodium current ( I Na.L ), transient sodium current ( I Na.T ), HERG current ( I HERG ), and Kv1.5 current ( I Kv1.5 ). The values of I Na.L , I Na.T , I HERG and I Kv1.5 were recorded using the whole-cell patch clamp technique. Compared with other channels, GFA showed selective blocking activity in late sodium channel. It inhibited I Na.L in a concentration-dependent manner with an IC 50 of (1.57 ± 0.14) μmol·L −1 , which was significantly lower than its IC 50 values of (21.17 ± 4.51) μmol·L −1 for the I Na.T . The inhibitory effect of GFA on I Na,L was not affected by 200 μmol·L −1 H 2 O 2 . It inhibited I HERG with an IC 50 of (273 ± 34) μmol·L −1 and has slight blocking effect on I Kv1.5 , decreasing I Kv1.5 by only 20.6% at 200 μmol·L −1 . In summary, GFA inhibited I Na.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.