Open AccessUp‐regulated Cx43 phosphorylation at Ser368 prolongs QRS duration in myocarditis
Author(s) -
Zhong Chunlian,
Chang He,
Wu Yang,
Zhou Li,
Wang Yan,
Wang Mingyan,
Wu Peng,
Qi Zhi,
Zou Jun
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13631
Subject(s) - qrs complex , connexin , mapk/erk pathway , medicine , p38 mitogen activated protein kinases , cardiology , myocarditis , duration (music) , phosphorylation , gap junction , biology , microbiology and biotechnology , intracellular , art , literature
Prolongation of QRS duration in electrocardiogram is one of the risk factors for morbidity and mortality in many kinds of cardiac diseases. However, its molecular mechanism is unknown. In this study, utilizing experimental autoimmune myocarditis ( EAM ) as a disease model, we show that the prolongation of QRS duration is accompanied by elevated phosphorylation of connexin 43 (Cx43) at Ser368 ( p S 368 Cx43). In cultured cells, inflammatory cytokine IL ‐1β activates p38 MAPK to up‐regulate p S 368 Cx43 and impairs cell‐to‐cell communication. In isolated hearts of normal rats, perfusion of IL ‐1β not only increases p S 368 Cx43 but also impairs cell‐to‐cell communication and prolongs QRS duration. Furthermore, blockade of p38 MAPK down‐regulates p S 368 Cx43, improves cell‐to‐cell communication and reduces QRS duration in EAM . These findings suggest that up‐regulation of p S 368 Cx43 by IL ‐1β via p38 MAPK contributes to the prolongation of QRS duration and could be a therapeutic target for myocarditis‐induced prolongation of QRS duration.