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A computational model of excitation and contraction in uterine myocytes from the pregnant rat

Aberrant uterine myometrial activities in humans are major health issues. However, the cellular and tissue mechanism(s) that maintain the uterine myometrium at rest during gestation, and that initiate and maintain long-lasting uterine contractions during delivery are incompletely understood. In this...

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Autores principales: Testrow, Craig P., Holden, Arun V., Shmygol, Anatoly, Zhang, Henggui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002389/
https://www.ncbi.nlm.nih.gov/pubmed/29904075
http://dx.doi.org/10.1038/s41598-018-27069-x
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author Testrow, Craig P.
Holden, Arun V.
Shmygol, Anatoly
Zhang, Henggui
author_facet Testrow, Craig P.
Holden, Arun V.
Shmygol, Anatoly
Zhang, Henggui
author_sort Testrow, Craig P.
collection PubMed
description Aberrant uterine myometrial activities in humans are major health issues. However, the cellular and tissue mechanism(s) that maintain the uterine myometrium at rest during gestation, and that initiate and maintain long-lasting uterine contractions during delivery are incompletely understood. In this study we construct a computational model for describing the electrical activity (simple and complex action potentials), intracellular calcium dynamics and mechanical contractions of isolated uterine myocytes from the pregnant rat. The model reproduces variant types of action potentials – from spikes with a smooth plateau, to spikes with an oscillatory plateau, to bursts of spikes – that are seen during late gestation under different physiological conditions. The effects of the hormones oestradiol (via reductions in calcium and potassium selective channel conductance), oxytocin (via an increase in intracellular calcium release) and the tocolytic nifedipine (via a block of L-type calcium channels currents) on action potentials and contractions are also reproduced, which quantitatively match to experimental data. All of these results validated the cell model development. In conclusion, the developed model provides a computational platform for further investigations of the ionic mechanism underlying the genesis and control of electrical and mechanical activities in the rat uterine myocytes.
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spelling pubmed-60023892018-06-26 A computational model of excitation and contraction in uterine myocytes from the pregnant rat Testrow, Craig P. Holden, Arun V. Shmygol, Anatoly Zhang, Henggui Sci Rep Article Aberrant uterine myometrial activities in humans are major health issues. However, the cellular and tissue mechanism(s) that maintain the uterine myometrium at rest during gestation, and that initiate and maintain long-lasting uterine contractions during delivery are incompletely understood. In this study we construct a computational model for describing the electrical activity (simple and complex action potentials), intracellular calcium dynamics and mechanical contractions of isolated uterine myocytes from the pregnant rat. The model reproduces variant types of action potentials – from spikes with a smooth plateau, to spikes with an oscillatory plateau, to bursts of spikes – that are seen during late gestation under different physiological conditions. The effects of the hormones oestradiol (via reductions in calcium and potassium selective channel conductance), oxytocin (via an increase in intracellular calcium release) and the tocolytic nifedipine (via a block of L-type calcium channels currents) on action potentials and contractions are also reproduced, which quantitatively match to experimental data. All of these results validated the cell model development. In conclusion, the developed model provides a computational platform for further investigations of the ionic mechanism underlying the genesis and control of electrical and mechanical activities in the rat uterine myocytes. Nature Publishing Group UK 2018-06-14 /pmc/articles/PMC6002389/ /pubmed/29904075 http://dx.doi.org/10.1038/s41598-018-27069-x Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Testrow, Craig P.
Holden, Arun V.
Shmygol, Anatoly
Zhang, Henggui
A computational model of excitation and contraction in uterine myocytes from the pregnant rat
title A computational model of excitation and contraction in uterine myocytes from the pregnant rat
title_full A computational model of excitation and contraction in uterine myocytes from the pregnant rat
title_fullStr A computational model of excitation and contraction in uterine myocytes from the pregnant rat
title_full_unstemmed A computational model of excitation and contraction in uterine myocytes from the pregnant rat
title_short A computational model of excitation and contraction in uterine myocytes from the pregnant rat
title_sort computational model of excitation and contraction in uterine myocytes from the pregnant rat
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002389/
https://www.ncbi.nlm.nih.gov/pubmed/29904075
http://dx.doi.org/10.1038/s41598-018-27069-x
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