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A myofibre model for the study of uterine excitation-contraction dynamics

As the uterus remodels in preparation for delivery, the excitability and contractility of the uterine smooth muscle layer, the myometrium, increase drastically. But when remodelling proceeds abnormally it can contribute to preterm birth, slow progress of labour, and failure to initiate labour. Remod...

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Autores principales: Goldsztejn, Uri, Nehorai, Arye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530703/
https://www.ncbi.nlm.nih.gov/pubmed/33004882
http://dx.doi.org/10.1038/s41598-020-72562-x
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author Goldsztejn, Uri
Nehorai, Arye
author_facet Goldsztejn, Uri
Nehorai, Arye
author_sort Goldsztejn, Uri
collection PubMed
description As the uterus remodels in preparation for delivery, the excitability and contractility of the uterine smooth muscle layer, the myometrium, increase drastically. But when remodelling proceeds abnormally it can contribute to preterm birth, slow progress of labour, and failure to initiate labour. Remodelling increases intercellular coupling and cellular excitability, which are the main targets of pharmaceutical treatments for uterine contraction disorders. However, the way in which electrical propagation and force development depend on intercellular coupling and cellular excitability is not fully understood. Using a computational myofibre model we study the dependency of electrical propagation and force development on intercellular coupling and cellular excitability. This model reveals that intercellular coupling determines the conduction velocity. Moreover, our model shows that intercellular coupling alone does not regulate force development. Further, cellular excitability controls whether conduction across the cells is blocked. Lastly, our model describes how cellular excitability regulates force development. Our results bridge cellular factors, targeted by drugs to regulate uterine contractions, and tissue level electromechanical properties, which are responsible for delivery. They are a step forward towards understanding uterine excitation-contraction dynamics and developing safer and more efficient pharmaceutical treatments for uterine contraction disorders.
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spelling pubmed-75307032020-10-02 A myofibre model for the study of uterine excitation-contraction dynamics Goldsztejn, Uri Nehorai, Arye Sci Rep Article As the uterus remodels in preparation for delivery, the excitability and contractility of the uterine smooth muscle layer, the myometrium, increase drastically. But when remodelling proceeds abnormally it can contribute to preterm birth, slow progress of labour, and failure to initiate labour. Remodelling increases intercellular coupling and cellular excitability, which are the main targets of pharmaceutical treatments for uterine contraction disorders. However, the way in which electrical propagation and force development depend on intercellular coupling and cellular excitability is not fully understood. Using a computational myofibre model we study the dependency of electrical propagation and force development on intercellular coupling and cellular excitability. This model reveals that intercellular coupling determines the conduction velocity. Moreover, our model shows that intercellular coupling alone does not regulate force development. Further, cellular excitability controls whether conduction across the cells is blocked. Lastly, our model describes how cellular excitability regulates force development. Our results bridge cellular factors, targeted by drugs to regulate uterine contractions, and tissue level electromechanical properties, which are responsible for delivery. They are a step forward towards understanding uterine excitation-contraction dynamics and developing safer and more efficient pharmaceutical treatments for uterine contraction disorders. Nature Publishing Group UK 2020-10-01 /pmc/articles/PMC7530703/ /pubmed/33004882 http://dx.doi.org/10.1038/s41598-020-72562-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Goldsztejn, Uri
Nehorai, Arye
A myofibre model for the study of uterine excitation-contraction dynamics
title A myofibre model for the study of uterine excitation-contraction dynamics
title_full A myofibre model for the study of uterine excitation-contraction dynamics
title_fullStr A myofibre model for the study of uterine excitation-contraction dynamics
title_full_unstemmed A myofibre model for the study of uterine excitation-contraction dynamics
title_short A myofibre model for the study of uterine excitation-contraction dynamics
title_sort myofibre model for the study of uterine excitation-contraction dynamics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530703/
https://www.ncbi.nlm.nih.gov/pubmed/33004882
http://dx.doi.org/10.1038/s41598-020-72562-x
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