The Carboxy Terminal Domain of Connexin43

Abstract

See related article, pages 1283–1291 Cardiac function depends fundamentally on gap junctions, plaques of transmembrane channels constructed from connexin proteins that bridge the plasma membranes of adjacent myocytes. By electrically coupling the entire myocyte population of the heart, these junctions preside over the cell-to-cell passage of the precisely orchestrated patterns of current flow that synchronize, coordinate, and harness individual cell contractions to generate the heart beat. In the ventricular myocardium, gap junctions are organized, together with 2 types of adhesion junction, the fasciae adherentes junctions and desmosomes, at the intercalated disks where the cell ends abut.1 The intercalated disk has a characteristic structure, exquisitely specialized for the task of integrating cell-to-cell electromechanical function (Figure). The fasciae adherentes junctions, which transmit mechanical force from cell to cell, link up the myofibrils of adjacent cells in series. They are thus, of necessity, situated in vertical zones of the disk. Because these vertical zones are staggered to varying extents, they are linked by membrane areas that lie parallel to the long axis of the cell. It is in these areas that the gap junctions are typically situated. Desmosomes, into which the desmin intermediate filaments of the cytoskeleton insert, form discrete “press-studs” predominantly (though not exclusively) located in the same membrane zones as the gap junctions. Larger gap junctions are commonly located at the disk periphery.2–4 Each junction type has thus traditionally been regarded as a spatially distinct entity with its own specialized function. Figure. Supramolecular organization of junctions at the intercalated disk. Light microscopy of ventricular myocardium (A) shows the disks as dense irregular dark lines (arrows), marking the boundaries between individual myocytes. If we take a single myocyte (between squared brackets), and view it at higher magnification by thin-section electron microscopy (B), the step-like features of the disks are …