Inhibitory effect of monoclonal antibody NCX-2D2 on isoproterenol-induced arrhythmias in adult rat hearts
10.3969/j.issn.1001-1978.2018.09.023
- VernacularTitle:钠-钙交换体单克隆抗体NCX-2D2对异丙肾上腺素诱发成年大鼠心律失常的抑制作用
- Author:
Xiao-Yan XUE
1
;
Miao-Miao WANG
;
Xiao-Lu WANG
;
Ming-Zhu YANG
;
Bo-Wei WU
;
Qi-Long FENG
Author Information
1. 山西医科大学生理学系
- Keywords:
Na+-Ca2+exchanger;
L-type calcium channel;
cardiac arrhythmia;
monoclonal antibody;
whole-cell patch clamp;
delayed afterdepolarization
- From:
Chinese Pharmacological Bulletin
2018;34(9):1308-1314
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effects of mono-clonal antibody NCX-2D2 on isoproterenol-induced ar-rhythmias in rat hearts, and to explore the electrophys-iological mechanism. Methods Using isoproterenol to establish in vitro and in vivo arrhythmic rat models to observe the effect of NCX-2D2 antibody on ventricular arrhythmias in rats. The whole-cell patch clamp tech-nique was used to investigate the effects of NCX-2D2 antibody on INa/Ca, ICa-Lat voltage-clamp mode and on DADs at current-clamp mode in single rat ventricular myocytes. Results 10 mg·L-1NCX-2D2 antibody significantly inhibited cardiac arrhythmias induced by ISO in vitro ( P<0.01) . 80 μg·kg-1NCX-2D2 anti-body markedly inhibit the occurrence of arrhythmias in ISO-induced anesthetized rats in vivo ( P <0.01 ) . 5 mg·L-1NCX-2D2 antibody partially inhibited the in-crease of INa/Ca(P<0.01) and the increase of ICa-L(P<0.01 ) , and could effectively inhibit ISO-induced DADs in rat ventricular myocytes ( P <0.05 ) . Con-clusions The sodium-calcium exchanger monoclonal antibody NCX-2D2 significantly inhibits isoproterenol-induced ventricular arrhythmias in rats. The mecha-nism against ventricular arrhythmias is mainly due to its inhibition of cardiomyocyte sodium-calcium exchanger and L-type calcium channel and marked suppression of DADs in rat ventricular myocytes.
