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:	Daisuke Sato, Donald M Bers, Yohannes Shiferaw
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9d0407ff7e804bf29b2ddcd2bdba9746
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spelling	oai:doaj.org-article:9d0407ff7e804bf29b2ddcd2bdba97462021-11-18T08:39:14ZFormation of spatially discordant alternans due to fluctuations and diffusion of calcium.1932-620310.1371/journal.pone.0085365https://doaj.org/article/9d0407ff7e804bf29b2ddcd2bdba97462013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24392005/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Spatially 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.Daisuke SatoDonald M BersYohannes ShiferawPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e85365 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daisuke Sato Donald M Bers Yohannes Shiferaw Formation of spatially discordant alternans due to fluctuations and diffusion of calcium.
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.
format	article
author	Daisuke Sato Donald M Bers Yohannes Shiferaw
author_facet	Daisuke Sato Donald M Bers Yohannes Shiferaw
author_sort	Daisuke Sato
title	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_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_sort	formation of spatially discordant alternans due to fluctuations and diffusion of calcium.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9d0407ff7e804bf29b2ddcd2bdba9746
work_keys_str_mv	AT daisukesato formationofspatiallydiscordantalternansduetofluctuationsanddiffusionofcalcium AT donaldmbers formationofspatiallydiscordantalternansduetofluctuationsanddiffusionofcalcium AT yohannesshiferaw formationofspatiallydiscordantalternansduetofluctuationsanddiffusionofcalcium
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Formation of spatially discordant alternans due to fluctuations and diffusion of calcium.

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