Refining the molecular organization of the cardiac intercalated disc

This review presents an extensively integrated model of the cardiac intercalated disc (ID), a highly orchestrated structure that connects adjacent cardiomyocytes. Classically, three main structures are distinguished: gap junctions (GJs) metabolically and electrically connect cytoplasm of adjacent cardiomyocytes; adherens junctions (AJs) connect the actin cytoskeleton of adjacent cells; and 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. However, rather than being independent, all ID components work together intensively by multifunctional proteins such as ZO-1, Ankyrin G, and β-catenin, integrating mechanical and electrical functions. 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. Lastly, this review integrates all these findings in comprehensible figures, illustrating the interdependencies of ID proteins.
Source: Cardiovascular Research - Category: Cardiology Source Type: research

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Conditions:   Chagas Cardiomyopathy;   Ventricular Arrythmia Interventions:   Procedure: Left trunk sympathectomy;   Procedure: Catheter ablation Sponsors:   University of Sao Paulo General Hospital;   Biosense Webster, Inc. Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Abstract Ankyrin-B (AnkB) is scaffolding protein that anchors integral membrane proteins to the cardiomyocyte cytoskeleton. We recently identified an AnkB variant, AnkB p.S646F (ANK2 c.1937 C>T) associated with a phenotype ranging from predisposition for cardiac arrhythmia to cardiomyopathy. AnkB p.S646F exhibited reduced expression levels in the H9c2 rat ventricular-derived cardiomyoblast cell line relative to wildtype AnkB. Here, we demonstrate that AnkB is regulated by proteasomal degradation and proteasome inhibition rescues AnkB p.S646F expression levels in H9c2 cells, although this effect is not conserved...
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Biochem Cell Biol Source Type: research
Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease, associated with ventricular arrhythmias, fibrofatty replacement of the myocardial mass and an increased risk of sudden cardiac death (SCD). Malignant ventricular arrhythmias and SCD largely occur in the pre-clinical phase of the disease, before overt structural changes occur. To prevent or interfere with ACM disease progression, more insight in mechanisms related to electrical instability are needed. Currently, numerous studies are focused on the link between cardiac arrhythmias and metabolic disease. In line with that, a potential role of mitochondrial dysfu...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
AbstractThe B cell lymphoma 2 –associated anthanogene (BAG3) is an anti-apoptotic co-chaperone protein. Previous reports suggest that mutations in BAG3 are associated with dilated cardiomyopathy. This review aims to summarize the current understanding of the relationship between BAG3 mutations and dilated cardiomyopathy, prima rily focusing on the role and protective mechanism of BAG3 in cardiomyocytes from individuals with dilated cardiomyopathy. The results of published studies show that BAG3 is critically important for reducing cardiomyocyte apoptosis, maintaining protein homeostasis, regulating mitochondrial stab...
Source: Heart Failure Reviews - Category: Cardiology Source Type: research
In conclusion, these findings indicate that CGL4 patients should also be carefully followed up for gastrointestinal and cardiac manifestations. PMID: 31778856 [PubMed - as supplied by publisher]
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
Publication date: Available online 19 November 2019Source: Pharmacological ResearchAuthor(s): Nebojša Mujović, Dobromir Dobrev, Milan Marinković, Vincenzo Russo, Tatjana S. PotparaAbstractAmiodarone is an iodinated benzofuran derivative, a highly lipophilic drug with unpredictable pharmacokinetics. Although originally classified as a class III agent due to its ability to prolong refractoriness in cardiac regions and prevent/terminate re-entry, amiodarone shows antiarrhythmic properties of all four antiarrhythmic drug classes. Amiodarone is a potent coronary and peripheral vasodilator and can be safely used in pati...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
We present a case of loperamide toxicity that has not been previously reported in the literature.
Source: The American Journal of Emergency Medicine - Category: Emergency Medicine Authors: Source Type: research
Authors: Mazkereth R, Maayan-Metzger A, Leibovitch L, Schushan-Eisen I, Morag I, Straus T Abstract BACKGROUND: The need for postnatal monitoring of infants exposed to intrauterine beta blockers (BBs) has not been clearly defined. OBJECTIVES: To evaluate infants exposed to intrauterine BBs in order to estimate the need for postnatal monitoring. METHODS: This retrospective case-control study comprised 153 term infants born to mothers who had been treated with BBs during pregnancy. Treatment indications included hypertension 76 mothers (49.7%), cardiac arrhythmias 48 (31.4%), rheumatic heart disease 14 (9.1%),...
Source: The Israel Medical Association Journal - Category: General Medicine Tags: Isr Med Assoc J Source Type: research
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