期刊
CARDIOVASCULAR RESEARCH
卷 113, 期 3, 页码 259-275出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvw259
关键词
Intercalated disc; Cardiac arrhythmia; Brugada syndrome; Arrhythmogenic cardiomyopathy; Wnt signaling
资金
- Netherlands CardioVascular Research Initiative
- Dutch Heart Foundation, Dutch Federation of University Medical Centres
- Netherlands Organisation for Health Research and Development
- Royal Netherlands Academy of Sciences (CVON-PREDICT)
This review presents an extensively integrated model of the cardiac intercalated disc (ID), a highly orchestrated structure that connects adjacent cardiomyocytes. Classically, three main structures are distinguished: gap junctions (GJs) metabolically and electrically connect cytoplasm of adjacent cardiomyocytes; adherens junctions (AJs) connect the actin cytoskeleton of adjacent cells; and desmosomes function as cell anchors and connect intermediate filaments. Furthermore, ion channels reside in the ID. Mutations in ID proteins have been associated with cardiac arrhythmias such as Brugada syndrome and arrhythmogenic cardiomyopathy. However, rather than being independent, all ID components work together intensively by multifunctional proteins such as ZO-1, Ankyrin G, and beta-catenin, integrating mechanical and electrical functions. GJs form a plaque surrounded by the perinexus in which free connexons reside; the connexome integrates Na-V channels, the desmosome and GJs; and the area composita hosts AJs and desmosomes, also integrated as adhering junctions. Furthermore, the transitional junction connects sarcomeres to the plasma membrane. Lastly, this review integrates all these findings in comprehensible figures, illustrating the interdependencies of ID proteins.
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