Antiarrhythmic ionic mechanism of Guanfu base A--Selective inhibition of late sodium current in isolated ventricular myocytes from guinea pigs.
10.1016/S1875-5364(15)30027-3
- Author:
Si-Si JIN
1
;
Qiao GUO
1
;
Jing XU
1
;
Peng YU
1
;
Jing-Han LIU
2
;
Yi-Qun TANG
3
Author Information
1. Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
2. Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
3. Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: tyq@cpu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Arrhythmia;
Guanfu base A;
Kv1.5 current;
Late sodium current;
Transient sodium current
- MeSH:
Analysis of Variance;
Animals;
Anti-Arrhythmia Agents;
pharmacology;
Dose-Response Relationship, Drug;
Female;
Guinea Pigs;
HEK293 Cells;
Heart Ventricles;
drug effects;
Heterocyclic Compounds, 4 or More Rings;
pharmacology;
Humans;
Inhibitory Concentration 50;
Male;
Membrane Potentials;
drug effects;
Myocytes, Cardiac;
metabolism;
Patch-Clamp Techniques;
Sodium Channel Blockers;
pharmacology;
Sodium Channels;
drug effects
- From:
Chinese Journal of Natural Medicines (English Ed.)
2015;13(5):361-367
- CountryChina
- Language:English
-
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.
