Antiarrhythmic ionic mechanism of Guanfu base A—Selective inhibition of late sodium current in isola

来源 :Chinese Journal of Natural Medicines | 被引量 : 0次 | 上传用户:deterly
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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 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 has an IC50 of (273 ± 34) μmol·L-1 and has a 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 retained similar inhibition in presence of reactive oxygen species. These findings may suggest a novel molecular mechanism for the potential clinical applica tion of GFA in the treatment of cardiovascular disorders.
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