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Cardiac remodeling and atrial fibrillation in transgenic miceoverexpressing junctin
Author(s) -
Hong ChangSoo,
Cho MyeongChan,
Kwak YongGeun,
Song ChangHo,
Lee YoungHoon,
Lim Jung Su,
Kwon Yunhee Kim,
Chae SooWan,
Kim Do Han
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0908fje
Subject(s) - calsequestrin , medicine , ryanodine receptor , endocrinology , endoplasmic reticulum , genetically modified mouse , transgene , biology , chemistry , receptor , microbiology and biotechnology , biochemistry , gene
Junctin is a 26‐kDa integral membrane protein, colocalized with the ryanodine receptor (RyR) and calsequestrin at the junctional sarcoplasmic reticulum (SR) membrane in cardiac and skeletal muscles. To elucidate the functional role of junctin in heart, transgenic (TG) mice overexpressing canine junctin (24–29 folds) under the control of mouse α‐myosin heavy chain promoter were generated. Overexpression of the junctin in mouse heart was associated with heart enlargements, bradycardia, atrial fibrillation, and increased fibrosis. Many ultrastructural alterations were observed in TG atria. The junctional SR cisternae facing transverse‐tubules contained a dense matrix of calsequestrin in TG heart. According to echocardiography, TG mice showed enlarged left ventricles, dilated right atriums, and ventricles with paradoxical septal motion and impaired left ventricular systolic function. Overexpression of junctin led to down‐regulation of triadin and RyR but to up‐regulation of dihydropyridine receptor. The L‐type Ca 2+ current density and action potential durations increased, which could be the cause for the bradycardia in TG heart. This study provides an important example of pathogenesis leading to substantial cardiac remodeling and atrial fibrillation, which was caused by overexpression of junctin in heart.