The intercalated disc (ID) is a highly specialized structure that connects cardiomyocytes via mechanical and electrical junctions. Although described in some detail by light microscopy in the 19th century, it was in 1966 that electron microscopy images showed that the ID represented apposing cell borders and provided detailed insight into the complex ID nanostructure. Since then, much has been learned about the ID and its molecular composition, and it has become evident that a large number of proteins, not all of them involved in direct cell-to-cell coupling via mechanical or gap junctions, reside at the ID. Furthermore, an increasing number of functional interactions between ID components are emerging, leading to the concept that the ID is not the sum of isolated molecular silos but an interacting molecular complex, an "organelle" where components work in concert to bring about electrical and mechanical synchrony. The aim of the present review is to give a short historical account of the ID's discovery and an updated overview of its composition and organization, followed by a discussion of the physiological implications of the ID architecture and the local intermolecular interactions. The latter will focus on both the importance of normal conduction of cardiac action potentials as well as the impact on the pathophysiology of arrhythmias.
Studies utilizing electron microscopy and live fluorescence microscopy have significantly enhanced our understanding of the molecular mechanisms that regulate junctional dynamics during homeostasis, development and disease. To fully grasp the enormous complexity of cell-cell adhesions, it is crucial to study the nanoscale architectures of tight junctions, adherens junctions and desmosomes. It is important to integrate these junctional architectures with the membrane morphology and cellular topography in which the junctions are embedded.
Becker muscular dystrophy (BMD) is a less severe X-linked genetic disorder caused by mutations in the DMD gene, resulting in truncated dystrophin and affecting muscle function, particularly in the heart.
Researchers created a rat model for BMD by deleting specific exons of the Dmd gene and evaluated the rats for functional and histopathological changes during their first year, finding moderate muscle damage and progressive heart disease.
RNA sequencing of cardiac tissue revealed shared abnormalities in BMD and Duchenne muscular dystrophy (DMD) rats, pointing to issues with key proteins at cell junctions, which could help understand dystrophin's role in muscle and heart function, and pave the way for new treatments.
Caveolin is a monotopic integral membrane protein, widely expressed in metazoa and responsible for constructing enigmatic membrane invaginations known as caveolae. Recently, the high-resolution structure of a purified human caveolin assembly, the CAV1-8S complex, revealed a unique organization of 11 protomers arranged in a tightly packed, radially symmetric spiral disc. One face and the outer rim of this disc are highly hydrophobic, suggesting that the complex incorporates into membranes by displacing hundreds of lipids from one leaflet.
Background: A structural heart disease or functional electrical abnormalities can cause an electrical storm.
Case Presentation: We present a young boy with an electrical storm who had no cardiac risk factors and a positive family history of sudden cardiac death. The stepwise diagnostic approach was ineffective in determining previously known causes as the origin of the electrical storm.
Background: Cardiac arrhythmias are the main cause of sudden death due to Chronic Chagasic Cardiomyopathy (CCC). Here we investigated alterations in connexin 43 (Cx43) expression and phosphorylation in cardiomyocytes as well as associations with cardiac arrhythmias in CCC.
Methods: C57Bl/6 mice infected with underwent cardiac evaluations at 6 and 12 months after infection via treadmill testing and EKG.
