Journal article
Remodeling of repolarization and arrhythmia susceptibility in a myosin-binding protein C knockout mouse model
American journal of physiology. Heart and circulatory physiology, v 313(3), pp H620-H630
01 Sep 2017
PMID: 28646025
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac diseases and among the leading causes of sudden cardiac death (SCD) in the young. The cellular mechanisms leading to SCD in HCM are not well known. Prolongation of the action potential (AP) duration (APD) is a common feature predisposing hypertrophied hearts to SCD. Previous studies have explored the roles of inward Na
and Ca
in the development of HCM, but the role of repolarizing K
currents has not been defined. The objective of this study was to characterize the arrhythmogenic phenotype and cellular electrophysiological properties of mice with HCM, induced by myosin-binding protein C (MyBPC) knockout (KO), and to test the hypothesis that remodeling of repolarizing K
currents causes APD prolongation in MyBPC KO myocytes. We demonstrated that MyBPC KO mice developed severe hypertrophy and cardiac dysfunction compared with wild-type (WT) control mice. Telemetric electrocardiographic recordings of awake mice revealed prolongation of the corrected QT interval in the KO compared with WT control mice, with overt ventricular arrhythmias. Whole cell current- and voltage-clamp experiments comparing KO with WT mice demonstrated ventricular myocyte hypertrophy, AP prolongation, and decreased repolarizing K
currents. Quantitative RT-PCR analysis revealed decreased mRNA levels of several key K
channel subunits. In conclusion, decrease in repolarizing K
currents in MyBPC KO ventricular myocytes contributes to AP and corrected QT interval prolongation and could account for the arrhythmia susceptibility.
Ventricular myocytes isolated from the myosin-binding protein C knockout hypertrophic cardiomyopathy mouse model demonstrate decreased repolarizing K
currents and action potential and QT interval prolongation, linking cellular repolarization abnormalities with arrhythmia susceptibility and the risk for sudden cardiac death in hypertrophic cardiomyopathy.
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Details
- Title
- Remodeling of repolarization and arrhythmia susceptibility in a myosin-binding protein C knockout mouse model
- Creators
- Amir Toib - St. Christopher's Hospital for ChildrenChen Zhang - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Giulia Borghetti - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Xiaoxiao Zhang - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, PennsylvaniaMarkus Wallner - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Yijun Yang - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Constantine D Troupes - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Hajime Kubo - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Thomas E Sharp - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Eric Feldsott - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Remus M Berretta - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Neil Zalavadia - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Danielle M Trappanese - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Shavonn Harper - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Polina Gross - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Xiongwen Chen - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Sadia Mohsin - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.Steven R Houser - Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
- Publication Details
- American journal of physiology. Heart and circulatory physiology, v 313(3), pp H620-H630
- Publisher
- American Physiological Society (APS)
- Grant note
- P01 HL091799 / NHLBI NIH HHS 15SDG25550038 / American Heart Association-American Stroke Association
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000412064100004
- Scopus ID
- 2-s2.0-85029389502
- Other Identifier
- 991019168637104721
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Peripheral Vascular Disease
- Physiology