|Keywords:||heart, arrhythmia, cardiology, ion channel, adherens junction, gap junction, desmosome, cytoskeleton, intercellular communication, connexin, cadherin, catenin, arrhythmogenic cardiomyopathy|
|Full text PDF:||http://dspace.library.uu.nl:8080/handle/1874/308917|
The intercalated disc is a highly orchestrated structure where two cardiomyocytes are connected. Three main structures can be distinguished. Gap junctions (GJs) metabolically and electrically connect cytoplasm of adjacent cardiomyocytes. Adherens junctions (AJs) connect the actin cytoskeleton of adjacent cells. 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. All ID components work together intensively by multifunctional proteins such as ZO-1, Ankyrin G and β-catenin. GJs form a plaque surrounded by the perinexus in which free connexons reside; the connexome integrates Nav 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. This thesis presents a model for the organisation of these ID structures, although many questions remain.