Apelin shorten QT interval by inhibiting Kir2.1/IK1 via a PI3K way in acute myocardial infarction
Apelin shorten QT interval by inhibiting Kir2.1/IK1 via a PI3K way in acute myocardial infarction
复制标题
Apelin 通过 PI3K 途径抑制 Kir2.1/IK1 缩短急性心肌梗死的 QT 间期。
DOI：
10.1016/j.bbrc.2019.07.041
复制
发表时间：
2019-09-17
影响因子：
3.1
通讯作者：
Shan, Hongli
中科院分区：
文献类型：
--
作者：
Li, Zhongrui;He, Qiufu;Shan, Hongli
QT interval prolongation and depolarization of resting membrane potential (RMP) were found in acute myocardial infarction (MI) which is involved in the arrhythmogenic mechanism and raising the risk to initiate torsade de pointes. However, clinical anti-arrhythmic agents that primarily act on QT interval and RMP are not currently available. Our objective was to determine whether Apelin, an endogenous peptide ligand of receptor APJ, affects QT interval and RMP and underlying mechanisms. To test this viewpoint, mice were subjected to MI by ligating the left main coronary artery and Apelin was applied through tail vein at 5 min prior coronary occlusion in tested group. Compared to MI group, pretreatment of Apelin (15 mu g/kg) shortened QTc and QT interval induced by MI, significantly elevated RMP and shortened action potential duration (APD) by increased I-k1 currents recorded using whole-cell patch technique from cardiomyocytes underwent MI. In cultured neonatal mouse cardiomyocytes, Apelin (1 mu mol/L) restored hypoxia-induced Kir2.1 down-regulation, which was abolished by IP3K inhibitor LY-294002. Additionally, Apelin elicited a time-dependent increase in phosphorylation of Alt leading to increase in PI3-kinase activity. These results showed that Apelin enhanced I-k1/Kir2.1 currents via IP3K pathway as by rescue ischemia- and hypoxia-induced RMP depolarization and prolongation of QT interval, which may prevent or cure acute ischemic-mediated arrhythmias. This study brings new information to antiarrhythmic theories and provides a potential target for the clinical management of acute ischemia-related arrhythmias. (C) 2019 Elsevier Inc. All rights reserved.
