Influence of transmural repolarization gradients on the electrophysiology and pharmacology of ventricular myocardium. Cellular basis for the Brugada and long–QT syndromes

Abstract

Restricted accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Antzelevitch C., Nesterenko V. V., Muzikant A. L., Rice J. J., Chen G. and Colatsky T. 2001Influence of transmural repolarization gradients on the electrophysiology and pharmacology of ventricular myocardium. Cellular basis for the Brugada and long–QT syndromesPhil. Trans. R. Soc. A.3591201–1216http://doi.org/10.1098/rsta.2001.0826SectionRestricted accessInfluence of transmural repolarization gradients on the electrophysiology and pharmacology of ventricular myocardium. Cellular basis for the Brugada and long–QT syndromes C. Antzelevitch C. Antzelevitch Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501, USA () Google Scholar Find this author on PubMed Search for more papers by this author , V. V. Nesterenko V. V. Nesterenko Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501, USA () Google Scholar Find this author on PubMed Search for more papers by this author , A. L. Muzikant A. L. Muzikant Physiome Sciences, 307 College Road, East Princeton, NJ 08540–6608, USA Google Scholar Find this author on PubMed Search for more papers by this author , J. J. Rice J. J. Rice Physiome Sciences, 307 College Road, East Princeton, NJ 08540–6608, USA Google Scholar Find this author on PubMed Search for more papers by this author , G. Chen G. Chen Physiome Sciences, 307 College Road, East Princeton, NJ 08540–6608, USA Google Scholar Find this author on PubMed Search for more papers by this author and T. Colatsky T. Colatsky Physiome Sciences, 307 College Road, East Princeton, NJ 08540–6608, USA Google Scholar Find this author on PubMed Search for more papers by this author C. Antzelevitch C. Antzelevitch Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501, USA () Google Scholar Find this author on PubMed Search for more papers by this author , V. V. Nesterenko V. V. Nesterenko Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501, USA () Google Scholar Find this author on PubMed Search for more papers by this author , A. L. Muzikant A. L. Muzikant Physiome Sciences, 307 College Road, East Princeton, NJ 08540–6608, USA Google Scholar Find this author on PubMed Search for more papers by this author , J. J. Rice J. J. Rice Physiome Sciences, 307 College Road, East Princeton, NJ 08540–6608, USA Google Scholar Find this author on PubMed Search for more papers by this author , G. Chen G. Chen Physiome Sciences, 307 College Road, East Princeton, NJ 08540–6608, USA Google Scholar Find this author on PubMed Search for more papers by this author and T. Colatsky T. Colatsky Physiome Sciences, 307 College Road, East Princeton, NJ 08540–6608, USA Google Scholar Find this author on PubMed Search for more papers by this author Published:15 June 2001https://doi.org/10.1098/rsta.2001.0826AbstractVentricular myocardium comprises at least three electrophysiologically distinct cell types: epicardial, endocardial and M cells. Epicardial and M cells, but not endocardial cells, display action potentials with a notched or spike–and–dome morphology: the result of a prominent, transient, outward current–mediated phase 1. M cells are distinguished from endocardial and epicardial cells by the ability of their action potential to disproportionately prolong in response to a slowing down of rate and/or in response to agents with class III actions. This intrinsic electrical heterogeneity contributes to the inscription of the electrocardiogram (ECG) as well as to the development of a variety of cardiac arrhythmias. Heterogeneous response of the three cell types to pharmacological agents and/or pathophysiological states results in amplification of intrinsic electrical heterogeneities, thus providing a substrate as well as a trigger for the development of re–entrant arrhythmias, including Torsade de Pointes, commonly associated with the long–QT syndrome (LQTS), and the polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF) encountered in the Brugada syndrome. Despite an abundance of experimental data describing the heterogeneity of cellular electrophysiology that exists across the ventricular wall, relatively few computer models have been developed to investigate the physiological and pathophysiological consequences of such electrical heterogeneity. As computer power increases and numerical algorithms improve, three–dimensional computer models of ventricular conduction that combine physiological membrane kinetics with realistic descriptions of myocardial structure and geometry will become more feasible. With sufficient detail and accuracy, these models should illuminate the complex mechanisms underlying the initiation and maintenance of Torsade de Pointes and other arrhythmias. Previous ArticleNext Article VIEW FULL TEXT DOWNLOAD PDF FiguresRelatedReferencesDetailsCited by Sabzpoushan S and Ghajarjazy A (2019) A method for reduction of human ventricular action potential model, Mathematical and Computer Modelling of Dynamical Systems, 10.1080/13873954.2019.1701039, 26:1, (1-30), Online publication date: 2-Jan-2020. 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