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Non-ohmic tissue conduction in cardiac electrophysiology: Upscaling the non-linear voltage-dependent conductance of gap junctions
Gap junctions are key mediators of intercellular communication in cardiac tissue, and their function is vital to sustaining normal cardiac electrical activity. Conduction through gap junctions strongly depends on the hemichannel arrangement and transjunctional voltage, rendering the intercellular co...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059938/ https://www.ncbi.nlm.nih.gov/pubmed/32097410 http://dx.doi.org/10.1371/journal.pcbi.1007232 |
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author | Hurtado, Daniel E. Jilberto, Javiera Panasenko, Grigory |
author_facet | Hurtado, Daniel E. Jilberto, Javiera Panasenko, Grigory |
author_sort | Hurtado, Daniel E. |
collection | PubMed |
description | Gap junctions are key mediators of intercellular communication in cardiac tissue, and their function is vital to sustaining normal cardiac electrical activity. Conduction through gap junctions strongly depends on the hemichannel arrangement and transjunctional voltage, rendering the intercellular conductance highly non-Ohmic, particularly under steady-state regimes of conduction. Despite this marked non-linear behavior, current tissue-level models of cardiac conduction are rooted in the assumption that gap-junctions conductance is constant (Ohmic), which results in inaccurate predictions of electrical propagation, particularly in the low junctional-coupling regime observed under pathological conditions. In this work, we present a novel non-Ohmic homogenization model (NOHM) of cardiac conduction that is suitable to tissue-scale simulations. Using non-linear homogenization theory, we develop a conductivity model that seamlessly upscales the voltage-dependent conductance of gap junctions, without the need of explicitly modeling gap junctions. The NOHM model allows for the simulation of electrical propagation in tissue-level cardiac domains that accurately resemble that of cell-based microscopic models for a wide range of junctional coupling scenarios, recovering key conduction features at a fraction of the computational complexity. A unique feature of the NOHM model is the possibility of upscaling the response of non-symmetric gap-junction conductance distributions, which result in conduction velocities that strongly depend on the direction of propagation, thus allowing to model the normal and retrograde conduction observed in certain regions of the heart. We envision that the NOHM model will enable organ-level simulations that are informed by sub- and inter-cellular mechanisms, delivering an accurate and predictive in-silico tool for understanding the heart function. Codes are available for download at https://github.com/dehurtado/NonOhmicConduction. |
format | Online Article Text |
id | pubmed-7059938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-70599382020-03-12 Non-ohmic tissue conduction in cardiac electrophysiology: Upscaling the non-linear voltage-dependent conductance of gap junctions Hurtado, Daniel E. Jilberto, Javiera Panasenko, Grigory PLoS Comput Biol Research Article Gap junctions are key mediators of intercellular communication in cardiac tissue, and their function is vital to sustaining normal cardiac electrical activity. Conduction through gap junctions strongly depends on the hemichannel arrangement and transjunctional voltage, rendering the intercellular conductance highly non-Ohmic, particularly under steady-state regimes of conduction. Despite this marked non-linear behavior, current tissue-level models of cardiac conduction are rooted in the assumption that gap-junctions conductance is constant (Ohmic), which results in inaccurate predictions of electrical propagation, particularly in the low junctional-coupling regime observed under pathological conditions. In this work, we present a novel non-Ohmic homogenization model (NOHM) of cardiac conduction that is suitable to tissue-scale simulations. Using non-linear homogenization theory, we develop a conductivity model that seamlessly upscales the voltage-dependent conductance of gap junctions, without the need of explicitly modeling gap junctions. The NOHM model allows for the simulation of electrical propagation in tissue-level cardiac domains that accurately resemble that of cell-based microscopic models for a wide range of junctional coupling scenarios, recovering key conduction features at a fraction of the computational complexity. A unique feature of the NOHM model is the possibility of upscaling the response of non-symmetric gap-junction conductance distributions, which result in conduction velocities that strongly depend on the direction of propagation, thus allowing to model the normal and retrograde conduction observed in certain regions of the heart. We envision that the NOHM model will enable organ-level simulations that are informed by sub- and inter-cellular mechanisms, delivering an accurate and predictive in-silico tool for understanding the heart function. Codes are available for download at https://github.com/dehurtado/NonOhmicConduction. Public Library of Science 2020-02-25 /pmc/articles/PMC7059938/ /pubmed/32097410 http://dx.doi.org/10.1371/journal.pcbi.1007232 Text en © 2020 Hurtado 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hurtado, Daniel E. Jilberto, Javiera Panasenko, Grigory Non-ohmic tissue conduction in cardiac electrophysiology: Upscaling the non-linear voltage-dependent conductance of gap junctions |
title | Non-ohmic tissue conduction in cardiac electrophysiology: Upscaling the non-linear voltage-dependent conductance of gap junctions |
title_full | Non-ohmic tissue conduction in cardiac electrophysiology: Upscaling the non-linear voltage-dependent conductance of gap junctions |
title_fullStr | Non-ohmic tissue conduction in cardiac electrophysiology: Upscaling the non-linear voltage-dependent conductance of gap junctions |
title_full_unstemmed | Non-ohmic tissue conduction in cardiac electrophysiology: Upscaling the non-linear voltage-dependent conductance of gap junctions |
title_short | Non-ohmic tissue conduction in cardiac electrophysiology: Upscaling the non-linear voltage-dependent conductance of gap junctions |
title_sort | non-ohmic tissue conduction in cardiac electrophysiology: upscaling the non-linear voltage-dependent conductance of gap junctions |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059938/ https://www.ncbi.nlm.nih.gov/pubmed/32097410 http://dx.doi.org/10.1371/journal.pcbi.1007232 |
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