Intercalated Disc: Changes in Multiple Proteins Associated with Heart Failure

The intercalated disc (ICD) occupies a central position in the transmission of force and electrical continuity between cardiomyocytes (CMs). Changes in its structure and composition strongly implicate heart failure with ICD. Its functions include: (1) the maintenance of electrical continuity across the ICD (gap junctions); (2) physically linking across the membranes and continuous with the cytoskeleton of adjacent CMs (desmosomes); (3) extracellular adherence between two cells (fascia adherens); and more recently (4) the addition of sarcomeres at the ICD during cell growth (the transitional junctions). The protein composition of each of these includes a much wider range of proteins than has been previously reported. Currently, 174 proteins have been associated with ICDs, approximately 42% of which are known to change in various heart diseases. This is the first comprehensive analysis, particularly focused on the proteins of the ICD that change in heart failure. Changes include: (1) membrane adhesion proteins (8 of 15 proteins);(2) cell anchoring, binding, and linking proteins (22 of 56 proteins); (3) channels (12 of 28 proteins); (4) enzymes (13 of 31 proteins); (5) ligands and ligand receptors (7 of 10 proteins); (6) other proteins that maintain the structure and functions of the ICD (3 of 8 proteins); (7) mechanoreceptors (4 of 5 proteins); and (8) 19 other proteins. Reports of changes in the relevant proteins (proteomics) can only be tested if there are corresponding antibodies available. Fortunately, 138 ICD proteins have corresponding antibodies of which 79% are commercially available. This will open the way for new strategies for dealing with human heart failure. We plan to