Journal article
Abstract 84: Remodeling of Repolarization and Arrhythmia Susceptibility in a Myosin Binding Protein C Knockout Mouse Model
Circulation research, v 119(suppl_1)
22 Jul 2016
Abstract
Abstract only
Background:
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease (1:500 in the general population) and amongst the leading causes of sudden cardiac death (SCD) in the young. There is lack of an in-depth understanding of cellular mechanisms leading to SCD in HCM. Prior studies that explored the cellular electrophysiological alterations in HCM, focused on the role of calcium and sodium currents in the development of cardiac hypertrophy and arrhythmia. Repolarizing potassium currents in HCM have not been investigated in detail. Better definition of the cellular substrates for arrhythmias could improve risk stratification and lead to potential novel therapeutic targets for prevention of SCD.
Objective:
To characterize the arrhythmogenic phenotype, cellular electrophysiological properties and repolarizing potassium currents in Myosin binding Protein C (MyBPC) knockout (KO) mice.
Methods and results:
MyBPC KO mice demonstrate overt phenotype with severe hypertrophy and cardiac dysfunction compared to wild type (WT) control mice, as evidenced by echocardiography and heart weight/body weight analysis. Telemetric electrocardiographic recordings reveal prolongation of the QTc interval in the KO compared to WT control mice (53.2 ± 7.4 vs 30.5 ± 5 msec, n=4 KO, 4 WT, p< 0.05) with frequent arrhythmias including preexcitation, ventricular and supraventricular tachycardia. Whole cell current and voltage clamp studies, comparing KO to WT mice, demonstrate myocyte hypertrophy (469 ± 44 vs 234 ± 15 pF, n=18 KO,15 WT, p<0.01), action potential prolongation (Action potential duration (APD)50 of 30.4± vs 17.7 msec, APD90 of 125.7± vs 74.7 msec, n=11 KO, 12 WT, p <0.05) and decreased repolarizing potassium currents (n=15 KO, 14 WT): I
k
Peak (-120 to 60 mV) decrease of 33-39%, I
k
1 (-120 to -60 mV) decrease of 16-30%, I
ks
(20 to 60 mV) decrease 21-23% and I
to
(0 to 60mV) decrease of 46-61%.
Conclusion:
MyBPC KO mice demonstrate remodeling of repolarizing potassium currents, action potential and QTc intervals prolongation that could account for the arrhythmia susceptibility.
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Details
- Title
- Abstract 84: Remodeling of Repolarization and Arrhythmia Susceptibility in a Myosin Binding Protein C Knockout Mouse Model
- Creators
- Amir Toib - Dexel Univ, Philadelphia, PASadia Mohsin - Temple UniversityXiaoxiao Zhang - Temple UniversityChen Zhang - Temple UniversityConstantine D Troupes - Temple UniversityMarkus Wallner - Temple UniversityRemus M Berretta - Temple UniversityThomas E Sharp - Temple UniversityGiulia Borghetti - Temple UniversityDanielle M Trappanese - Temple UniversityXiongwen Chen - Temple UniversitySteven R Houser - Temple University
- Publication Details
- Circulation research, v 119(suppl_1)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Other Identifier
- 991021862311104721