Alk7 Depleted Mice Exhibit Prolonged Cardiac Repolarization and Are Predisposed to Ventricular Arrhythmia

作者：Ying, Shaozhen; Cao, Hong; Hu, He; Wang, Xin; Tang, Yanhong; Huang, Congxin^*

来源：PLos One, 2016, 11(2): e0149205.

DOI：10.1371/journal.pone.0149205

• MYOCARDIAL ISCHEMIA/REPERFUSION INJURY
• LONG QT SYNDROME
• K+ CHANNEL
• ADIPOSE-TISSUE
• X-RECEPTOR
• I-TO
• APOPTOSIS
• PROTECTS
• CELLS
• PATHOGENESIS

We aimed to investigate the role of activin receptor-like kinase (ALK7) in regulating cardiac electrophysiology. Here, we showed that Alk7(-/-) mice exhibited prolonged QT intervals in telemetry ECG recordings. Furthermore, Langendorff-perfused Alk7(-/-) hearts had significantly longer action potential duration (APD) and greater incidence of ventricular arrhythmia (AV) induced by burst pacing. Using whole-cell patch clamp, we found that the densities of repolarizing K+ currents I-to and I-K1 were profoundly reduced in Alk7(-/-) ventricular cardiomyocytes. Mechanistically, the expression of Kv4.2 (a major subunit of I-to carrying channel) and KCHIP2 (a key accessory subunit of I-to carrying channel), was markedly decreased in Alk7(-/-) hearts. These findings suggest that endogenous expression of ALK7 is necessary to maintain repolarizing K+ currents in ventricular cardiomyocytes, and finally prevent action potential prolongation and ventricular arrhythmia.

• 出版日期2016-2-16
• 单位武汉大学