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

作　　者：JIN Si-Si GUO Qiao XU Jing YU Peng LIU Jing-Han TANG Yi-Qun 

机构地区：[1]Research Division of Pharmacology,China Pharmaceutical University [2]Department of Natural Medicinal Chemistry,China Pharmaceutical University

出　　处：《Chinese Journal of Natural Medicines》2015年第5期361-367,共7页中国天然药物（英文版）

基　　金：supported by the Fundamental Research Funds for the Central Universities(No.JKZ2011007);the National "Key Program for New Drug Research Development"(No.2009 ZX09103-345)

摘　　要：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 200μmol·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.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.

关 键 词：Guanfu base A Late sodium current Transient sodium current Kv1.5 current ARRHYTHMIA 

分 类 号：R965[医药卫生—药理学]