title: 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 (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.
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Jin
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jing-Han
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: tyq@cpu.edu.cn.
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Tang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D057809:HEK293 Cells; D006352:Heart Ventricles / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C040615:Guan-fu base A
keywords: Arrhythmia; Guanfu base A; Kv1.5 current; Late sodium current; Transient sodium current