Referenced in: none

Automatically associated channels: Kv1.5 , Kv11.1

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

Authors: Si-Si Jin, Qiao Guo, Jing Xu, Peng Yu, Jing-Han Liu, Yi-Qun Tang

Journal, date & volume: Chin J Nat Med, 2015 May , 13, 361-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25986285

Abstract
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 IC50 values of (21.17 ± 4.51) μmol · L(-1) for the INa.T. The inhibitory effect of GFA on INa,L was not affected by 200 μmol · L(-1) H2O2. It inhibited IHERG with an IC50 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.