Arrhythmogenic substrates in myocardial infarct
- 1 September 2008
- journal article
- review article
- Published by Wiley in Pathology International
- Vol. 58 (9), 533-543
- https://doi.org/10.1111/j.1440-1827.2008.02269.x
Abstract
Life-threatening ventricular tachyarrhythmias are common clinical complications in ischemic heart diseases, especially infarcted heart. Although electrophysiological mechanisms have been extensively clarified for the genesis of arrhythmias in myocardial infarct, arrhythmogenic substrates in the infarct that eventually lead to electrical derangements are not fully understood. This review focuses on the intracellular calcium ion (Ca2+) dynamics and connexin43 (Cx43) gap junctions that play pivotal roles in excitation/contraction processes and intercellular communication, respectively, in heart muscle cells. Recent development of Ca2+-sensitive fluorescent dyes as well as microscopy imaging techniques has contributed substantially to a more precise understanding of spatiotemporal aspects in the intra- and inter-cellular dynamics of Ca2+ in cardiomyocytes. Ca2+ waves, heterogeneous wave-like elevations of the intracellular Ca2+ concentrations ([Ca2+](i)) that develop under [Ca2+](i)-overloaded conditions of the injured myocardium, play an essential role in arrhythmias, especially in triggered arrhythmias. Alteration of Cx43-mediated electrical coupling, that is, gap junction remodeling that arises at myocyte-myocyte and myocyte-myofibroblast interfaces, would also be an important substrate for arrhythmias, especially re-entrant tachyarrhythmias. Clarification of these substrates would provide not only deeper insights into the upstream events of life-threatening tachyarrhythmias in the infarcted heart but also bases for new therapeutic strategies for cardiovascular diseases.Keywords
This publication has 56 references indexed in Scilit:
- Burst Emergence of Intracellular Ca 2+ Waves Evokes Arrhythmogenic Oscillatory Depolarization via the Na + –Ca 2+ ExchangerCirculation Research, 2008
- Connexin43 Knockdown Accelerates Wound Healing but Inhibits Mesenchymal Transition after Corneal Endothelial Injury In VivoInvestigative Ophthalmology & Visual Science, 2008
- Cx43 Mediates TGF-β Signaling through Competitive Smads Binding to MicrotubulesMolecular Biology of the Cell, 2007
- In situ Ca2+ dynamics of Purkinje fibers and its interconnection with subjacent ventricular myocytesJournal of Molecular and Cellular Cardiology, 2005
- Toward an Integrated Understanding of the Purkinje Fibers in the Heart: The Functional and Morphological Interconnection between the Purkinje Fibers and Ventricular MuscleACTA HISTOCHEMICA ET CYTOCHEMICA, 2005
- Spatiotemporal Visualization of Intracellular Ca2+ in Living Heart Muscle Cells Viewed by Confocal Laser Scanning Microscopy.ACTA HISTOCHEMICA ET CYTOCHEMICA, 2003
- Signal Transduction by the TGF-β SuperfamilyScience, 2002
- Calcium Extrusion During Aftercontractions in Cardiac Myocytes: The Role of the Sodium-calcium Exchanger in the Generation of the Transient Inward CurrentJournal of Molecular and Cellular Cardiology, 2000
- Scrape-loading and dye transfer: A rapid and simple technique to study gap junctional intercellular communicationExperimental Cell Research, 1987
- Synchronized beating of embryonic mouse myocardial cells mediated by FL cells in monolayer cultureExperimental Cell Research, 1969