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Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium

Spatially discordant alternans (SDA) of action potential duration (APD) is a phenomenon where different regions of cardiac tissue exhibit an alternating sequence of APD that are out-of-phase. SDA is arrhythmogenic since it can induce spatial heterogeneity of refractoriness, which can cause wavebreak...

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Autores principales: Sato, Daisuke, Bers, Donald M., Shiferaw, Yohannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877395/
https://www.ncbi.nlm.nih.gov/pubmed/24392005
http://dx.doi.org/10.1371/journal.pone.0085365
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author Sato, Daisuke
Bers, Donald M.
Shiferaw, Yohannes
author_facet Sato, Daisuke
Bers, Donald M.
Shiferaw, Yohannes
author_sort Sato, Daisuke
collection PubMed
description Spatially discordant alternans (SDA) of action potential duration (APD) is a phenomenon where different regions of cardiac tissue exhibit an alternating sequence of APD that are out-of-phase. SDA is arrhythmogenic since it can induce spatial heterogeneity of refractoriness, which can cause wavebreak and reentry. However, the underlying mechanisms for the formation of SDA are not completely understood. In this paper, we present a novel mechanism for the formation of SDA in the case where the cellular instability leading to alternans is caused by intracellular calcium (Ca) cycling, and where Ca transient and APD alternans are electromechanically concordant. In particular, we show that SDA is formed when rapidly paced cardiac tissue develops alternans over many beats due to Ca accumulation in the sarcoplasmic reticulum (SR). The mechanism presented here relies on the observation that Ca cycling fluctuations dictate Ca alternans phase since the amplitude of Ca alternans is small during the early stages of pacing. Thus, different regions of a cardiac myocyte will typically develop Ca alternans which are opposite in phase at the early stages of pacing. These subcellular patterns then gradually coarsen due to interactions with membrane voltage to form steady state SDA of voltage and Ca on the tissue scale. This mechanism for SDA is distinct from well-known mechanisms that rely on conduction velocity restitution, and a Turing-like mechanism known to apply only in the case where APD and Ca alternans are electromechanically discordant. Furthermore, we argue that this mechanism is robust, and is likely to underlie a wide range of experimentally observed patterns of SDA.
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spelling pubmed-38773952014-01-03 Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium Sato, Daisuke Bers, Donald M. Shiferaw, Yohannes PLoS One Research Article Spatially discordant alternans (SDA) of action potential duration (APD) is a phenomenon where different regions of cardiac tissue exhibit an alternating sequence of APD that are out-of-phase. SDA is arrhythmogenic since it can induce spatial heterogeneity of refractoriness, which can cause wavebreak and reentry. However, the underlying mechanisms for the formation of SDA are not completely understood. In this paper, we present a novel mechanism for the formation of SDA in the case where the cellular instability leading to alternans is caused by intracellular calcium (Ca) cycling, and where Ca transient and APD alternans are electromechanically concordant. In particular, we show that SDA is formed when rapidly paced cardiac tissue develops alternans over many beats due to Ca accumulation in the sarcoplasmic reticulum (SR). The mechanism presented here relies on the observation that Ca cycling fluctuations dictate Ca alternans phase since the amplitude of Ca alternans is small during the early stages of pacing. Thus, different regions of a cardiac myocyte will typically develop Ca alternans which are opposite in phase at the early stages of pacing. These subcellular patterns then gradually coarsen due to interactions with membrane voltage to form steady state SDA of voltage and Ca on the tissue scale. This mechanism for SDA is distinct from well-known mechanisms that rely on conduction velocity restitution, and a Turing-like mechanism known to apply only in the case where APD and Ca alternans are electromechanically discordant. Furthermore, we argue that this mechanism is robust, and is likely to underlie a wide range of experimentally observed patterns of SDA. Public Library of Science 2013-12-31 /pmc/articles/PMC3877395/ /pubmed/24392005 http://dx.doi.org/10.1371/journal.pone.0085365 Text en © 2013 Sato et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sato, Daisuke
Bers, Donald M.
Shiferaw, Yohannes
Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium
title Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium
title_full Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium
title_fullStr Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium
title_full_unstemmed Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium
title_short Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium
title_sort formation of spatially discordant alternans due to fluctuations and diffusion of calcium
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877395/
https://www.ncbi.nlm.nih.gov/pubmed/24392005
http://dx.doi.org/10.1371/journal.pone.0085365
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