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,I...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.展开更多
基金This work was supported by the grant from the National Natural Science Foundation of China （grant number. No： 81030002,81170177, 81100215, 81373835）.
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)
文摘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.
