Investigation of effects of monoclonal antibody NCX-3F10against Na+/Ca2+ exchanger on rat cardiac ionic currentsand its suppression on ischemia-reperfusion induced cardiac arrhythmias
10.3969/j.issn.1001-1978.2017.07.010
- VernacularTitle:钠-钙交换体单克隆抗体NCX-3F10对大鼠心室肌主要离子电流的影响及对缺血/再灌注诱发心律失常的抑制作用
- Author:
Mingzhu YANG
;
Yichun CHEN
;
Xiaolu WANG
;
Yuqi ZHANG
;
Xiaoyan XUE
;
Qilong FENG
;
Bowei WU
- Keywords:
Na+-Ca2+ exchanger;
monoclonal antibody;
whole-cell patch clamp technique;
ion current;
cardiac arrhythmia;
ischemia-reperfusion
- From:
Chinese Pharmacological Bulletin
2017;33(7):934-941
- CountryChina
- Language:Chinese
-
Abstract:
Aim To observe the effect of antibody NCX-3F10 on the main ion current of rat ventricular myocytes and its effect on arrhythmias induced by ischemia/reperfusion(I/R).Methods ① The whole-cell patch clamp technique was employed to record the Na+/Ca2+ exchange current(INa/Ca) and other major ion currents in rat ventricular myocytes.② The rat models of arrhythmia induced by ischemia/reperfusion were established by ligating the left coronary artery to in vivo and in vitro.Then the effects of antibody on the arrhythmia were observed.③ The IonOptix ion imaging system was used to observe the effect of antibody on calcium transients in single ventricular myocytes.Results ① The antibody NCX-3F10 dose-dependently inhibited INa/Ca from 5 to 40 mg·L-1.The IC50 for outward and inward currents was 11.15 and 11.69 mg·L-1, and the maximum inhibitory rates were 61% and 62%, respectively.The antibody also had an inhibitory effect on calcium current(ICa-L), and had no significant effect on inward rectifier potassium current(IK1), transient outward potassium current(Ito) and sodium current(INa).② In the isolated rat heart group I/R, 100% rats showed ventricular tachycardia, and 88.89% rats had ventricular fibrillation.After administration of antibody NCX-3F10(10 mg·L-1) 5 min before reperfusion, the incidence of ventricular tachycardia decreased to 44.43%(P<0.05), and the duration of ventricular tachycardia and ventricular fibrillation was also shortened remarkably(P<0.05).③ In the anesthetized rats after administration of antibody NCX-3F10(50 μg·kg-1) 5 min before reperfusion, the incidence and duration of ventricular tachycardia,the incidence and duration of ventricular fibrillation, and total number of ventricular premature beats were significantly decreased(P<0.05).④ From 5 to 40 mg·L-1, NCX-3F10 antibody decreased calcium transient amplitude in rat single ventricular myocytes dose-dependently(P<0.05).Conclusions The NCX-3F10 antibody shows significant arrhythmic effects on ischemia-reperfusion induced arrhythmia in rats both in vitro and in vivo, the underlying mechanism of which is related to NCX and L-type calcium current inhibition and calcium overload reduction by the NCX antibody.
