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

Shaozhen Ying; Hong Cao; He Hu; Xin Wang; Yanhong Tang; Congxin Huang

doi:10.1371/journal.pone.0149205

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

PLoS One. 2016 Feb 16;11(2):e0149205. doi: 10.1371/journal.pone.0149205. eCollection 2016.

Authors

Shaozhen Ying¹, Hong Cao¹, He Hu¹, Xin Wang¹, Yanhong Tang¹, Congxin Huang¹

Affiliation

¹ Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China, 238 Jiefang Road, Wuchang District, Wuhan 430060, Hubei Province, China.

Abstract

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 Ito and IK1 were profoundly reduced in Alk7-/- ventricular cardiomyocytes. Mechanistically, the expression of Kv4.2 (a major subunit of Ito carrying channel) and KCHIP2 (a key accessory subunit of Ito 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials*
Activin Receptors, Type I / deficiency*
Activin Receptors, Type I / metabolism
Animals
Arrhythmias, Cardiac / diagnostic imaging
Arrhythmias, Cardiac / metabolism
Arrhythmias, Cardiac / physiopathology*
Cell Separation
Disease Susceptibility
Electrocardiography
Heart Ventricles / diagnostic imaging
Heart Ventricles / pathology
Heart Ventricles / physiopathology*
In Vitro Techniques
Mice, Inbred C57BL
Myocytes, Cardiac / metabolism
Myocytes, Cardiac / pathology
Perfusion
Potassium Channels, Tandem Pore Domain / metabolism
Protein Subunits / metabolism
Telemetry
Ultrasonography

Substances

Potassium Channels, Tandem Pore Domain
Protein Subunits
Activin Receptors, Type I
Acvr1c protein, mouse

Grants and funding

This study is supported by funding from The National Science Technology Support Plan (Grant No. 2011BAI11B12) and the National Natural Science Foundation of China (Grant No. 81370282). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.