Antiarrhythmic ionic mechanism of Guanfu base A--Selective inhibition of late sodium current in isolated ventricular myocytes from guinea pigs / 中国天然药物
Chinese Journal of Natural Medicines (English Ed.)
;
(6): 361-367, 2015.
Article
in English
| WPRIM
| ID: wpr-812134
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Sodium Channels
/
Analysis of Variance
/
Patch-Clamp Techniques
/
Inhibitory Concentration 50
/
Sodium Channel Blockers
/
Myocytes, Cardiac
/
Dose-Response Relationship, Drug
/
HEK293 Cells
/
Guinea Pigs
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Chinese Journal of Natural Medicines (English Ed.)
Year:
2015
Type:
Article
Similar
MEDLINE
...
LILACS
LIS