Effect of sophocarpine on HERG K+ channels.
- Author:
Zhi-Ping QI
1
;
Shan-Shan SHI
;
Xue-Ling ZHAO
;
Wen-Xiao ZHAO
;
Yun-Long BAI
;
Yan-Jie LÜ
;
Bao-Xin LI
;
Bao-Feng YANG
Author Information
1. Department of Pharmacology, Bio-pharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory, Harbin Medical University, Harbin 150086, China.
- Publication Type:Journal Article
- MeSH:
Alkaloids;
pharmacology;
Anti-Arrhythmia Agents;
pharmacology;
Cell Line;
Dose-Response Relationship, Drug;
Ether-A-Go-Go Potassium Channels;
antagonists & inhibitors;
metabolism;
physiology;
Humans;
Kidney;
cytology;
Kinetics;
Membrane Potentials;
drug effects;
Patch-Clamp Techniques;
Plants, Medicinal;
chemistry;
Sophora;
chemistry
- From:
Acta Pharmaceutica Sinica
2008;43(1):44-49
- CountryChina
- Language:Chinese
-
Abstract:
Human ether-a-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier K+ current, which has an important effect on both proarrhythmia and antiarrhythmia. To investigate the effect of sophocarpine (SC) on HERG channel stably expressing in human embryonic kidney-293 (HEK293) cells, whole-cell patch-clamp technique was used to record HERG current and kinetic curves. As the result, it was found that SC inhibited HERG current in a concentration-dependent manner (10, 30, 100, and 300 micromol x L(-1)). At 0 mV, 10, 30, 100, and 300 micromol x L(-1) SC respectively inhibited IHERG by Istep ( 10.7 +/- 2.8)% , (11.3 +/- 5.5)% , (47.0 +/- 2.3)% and (53.7 +/- 2.5)% , and Itail (1.1 +/- 3.0)%, (17.1 +/- 3.3)%, (32.7 +/- 1.9)% (P < 0.05, n = 12) and (56.0 +/- 2.4)% (P < 0.05, n = 13). The time constants of inactivation, recovery from inactivation and onset of inactivation were accelerated. SC did not change other channel kinetics (activation and deactivation). It is concluded that SC inhibited the transfected HERG channels by influencing the inactivation state, which is the probable anti-arrhythmic mechanism.
