title: Alk7 Depleted Mice Exhibit Prolonged Cardiac Repolarization and Are Predisposed to Ventricular Arrhythmia.
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.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China, 238 Jiefang Road, Wuchang District, Wuhan 430060, Hubei Province, China.
authors.forename: Shaozhen
authors.initials: S
authors.lastname: Ying
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China, 238 Jiefang Road, Wuchang District, Wuhan 430060, Hubei Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China, 238 Jiefang Road, Wuchang District, Wuhan 430060, Hubei Province, China.
authors.forename: He
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China, 238 Jiefang Road, Wuchang District, Wuhan 430060, Hubei Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China, 238 Jiefang Road, Wuchang District, Wuhan 430060, Hubei Province, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China, 238 Jiefang Road, Wuchang District, Wuhan 430060, Hubei Province, China.
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D000200:Action Potentials; D030201:Activin Receptors, Type I / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D002469:Cell Separation; D004198:Disease Susceptibility; D004562:Electrocardiography; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D010477:Perfusion; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D013686:Telemetry; D014463:Ultrasonography
chemical_list: D024683:Potassium Channels, Tandem Pore Domain; D021122:Protein Subunits; D030201:Activin Receptors, Type I; C515277:Acvr1c protein, mouse