Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.

Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca²+ dynamics, which differ...

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Autores principales:	Jussi T Koivumäki, Topi Korhonen, Pasi Tavi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b9ea382be02c455d9c27cdf917a402bf
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spelling	oai:doaj.org-article:b9ea382be02c455d9c27cdf917a402bf2021-11-18T05:50:46ZImpact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.1553-734X1553-735810.1371/journal.pcbi.1001067https://doaj.org/article/b9ea382be02c455d9c27cdf917a402bf2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21298076/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca²+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL) ion currents, accounts for the heterogeneity of intracellular Ca²+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR). Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca²+ dynamics: 1) the biphasic increment during the upstroke of the Ca²+ transient resulting from the delay between the peripheral and central SR Ca²+ release, and 2) the relative contribution of SL Ca²+ current and SR Ca²+ release to the Ca²+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca²+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca²+ release sites define the interface between Ca²+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca²+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca²+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca²+ signaling. Thus, the model provides a useful framework for future studies of excitation-contraction coupling in human atrial myocytes.Jussi T KoivumäkiTopi KorhonenPasi TaviPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 1, p e1001067 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Jussi T Koivumäki Topi Korhonen Pasi Tavi Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.
description	Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca²+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL) ion currents, accounts for the heterogeneity of intracellular Ca²+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR). Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca²+ dynamics: 1) the biphasic increment during the upstroke of the Ca²+ transient resulting from the delay between the peripheral and central SR Ca²+ release, and 2) the relative contribution of SL Ca²+ current and SR Ca²+ release to the Ca²+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca²+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca²+ release sites define the interface between Ca²+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca²+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca²+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca²+ signaling. Thus, the model provides a useful framework for future studies of excitation-contraction coupling in human atrial myocytes.
format	article
author	Jussi T Koivumäki Topi Korhonen Pasi Tavi
author_facet	Jussi T Koivumäki Topi Korhonen Pasi Tavi
author_sort	Jussi T Koivumäki
title	Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.
title_short	Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.
title_full	Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.
title_fullStr	Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.
title_full_unstemmed	Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.
title_sort	impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b9ea382be02c455d9c27cdf917a402bf
work_keys_str_mv	AT jussitkoivumaki impactofsarcoplasmicreticulumcalciumreleaseoncalciumdynamicsandactionpotentialmorphologyinhumanatrialmyocytesacomputationalstudy AT topikorhonen impactofsarcoplasmicreticulumcalciumreleaseoncalciumdynamicsandactionpotentialmorphologyinhumanatrialmyocytesacomputationalstudy AT pasitavi impactofsarcoplasmicreticulumcalciumreleaseoncalciumdynamicsandactionpotentialmorphologyinhumanatrialmyocytesacomputationalstudy
_version_	1718424811390107648

Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.

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