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Dependence of Electrical Coupling on Mechanical Coupling in Cardiac Myocytes: Insights Gained from Cardiomyopathies Caused by Defects in Cell‐Cell Connections
Author(s) -
SAFFITZ JEFFREY E.
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1341.030
Subject(s) - gap junction , myocyte , desmoplakin , plakoglobin , cell junction , intracellular , intercalated disc , cardiac myocyte , coupling (piping) , adhesion , microbiology and biotechnology , cell adhesion , cell–cell interaction , chemistry , materials science , cell , biology , signal transduction , biochemistry , wnt signaling pathway , organic chemistry , catenin , metallurgy
A bstract : Cardiac myocytes are electrically coupled by large gap junctions to ensure safe conduction. Membrane regions containing gap junction channels are rigid and susceptible to fragmentation in response to shear stress. Thus, gap junctions in cardiac myocytes are located in close proximity to points of cell‐cell adhesion within the intercalated disk. These adhesion junctions mechanically stabilize the sarcolemmas of adjacent cells to allow formation and maintenance of large arrays of intercellular channels. It has been proposed that the extent to which cardiac myocytes are coupled mechanically at cell‐cell adhesion junctions is an important determinant of the extent to which cells can become electrically coupled at gap junctions. This hypothesis has been tested by analyzing gap junctions in human cardiomyopathies caused by mutations in plakoglobin and desmoplakin, intracellular proteins that link adhesion molecules at cell‐cell junctions to the cardiac myocyte cytoskeleton. Marked remodeling of cardiac gap junctions, despite the presence of normal intracellular levels of connexin43, was observed. This suggests that defects in cell‐cell adhesion, or the presence of discontinuities between adhesion junctions and the cytoskeleton, destabilize gap junctions and diminish electrical coupling. This could contribute to the high incidence of ventricular arrhythmias and sudden death known to occur in these cardiomyopathies.