作者
David L Beavers, Wei Wang, Sameer Ather, Niels Voigt, Alejandro Garbino, Sayali S Dixit, Andrew P Landstrom, Na Li, Qiongling Wang, Iacopo Olivotto, Dobromir Dobrev, Michael J Ackerman, Xander HT Wehrens
发表日期
2013/11/19
期刊
Journal of the American College of Cardiology
卷号
62
期号
21
页码范围
2010-2019
出版商
American College of Cardiology Foundation
简介
Objectives
This study sought to study the role of junctophilin-2 (JPH2) in atrial fibrillation (AF).
Background
JPH2 is believed to have an important role in sarcoplasmic reticulum (SR) Ca2+ handling and modulation of ryanodine receptor Ca2+ channels (RyR2). Whereas defective RyR2-mediated Ca2+ release contributes to the pathogenesis of AF, nothing is known about the potential role of JPH2 in atrial arrhythmias.
Methods
Screening 203 unrelated hypertrophic cardiomyopathy patients uncovered a novel JPH2 missense mutation (E169K) in 2 patients with juvenile-onset paroxysmal AF (pAF). Pseudoknock-in (PKI) mouse models were generated to determine the molecular defects underlying the development of AF caused by this JPH2 mutation.
Results
PKI mice expressing E169K mutant JPH2 exhibited a higher incidence of inducible AF than wild type (WT)-PKI mice, whereas A399S-PKI mice expressing a …
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DL Beavers, W Wang, S Ather, N Voigt, A Garbino… - Journal of the American College of Cardiology, 2013