A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.

Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-c...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wing-Chiu Tong, Cecilia Y Choi, Sanjay Kharche, Arun V Holden, Henggui Zhang, Michael J Taggart
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/52d14292fc0746fdaad5e71a8e850025
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:52d14292fc0746fdaad5e71a8e850025
record_format	dspace
spelling	oai:doaj.org-article:52d14292fc0746fdaad5e71a8e8500252021-11-18T06:54:37ZA computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.1932-620310.1371/journal.pone.0018685https://doaj.org/article/52d14292fc0746fdaad5e71a8e8500252011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21559514/?tool=EBIhttps://doaj.org/toc/1932-6203Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca2+ currents (L- and T-type), Na+ current, an hyperpolarization-activated current, three voltage-gated K+ currents, two Ca2+-activated K+ current, Ca2+-activated Cl current, non-specific cation current, Na+-Ca2+ exchanger, Na+-K+ pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular Ca2+ computed from known Ca2+ fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing [Ca2+]i. This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, [Ca2+]i and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical E-C coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels.Wing-Chiu TongCecilia Y ChoiSanjay KharcheArun V HoldenHenggui ZhangMichael J TaggartPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18685 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wing-Chiu Tong Cecilia Y Choi Sanjay Kharche Arun V Holden Henggui Zhang Michael J Taggart A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.
description	Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca2+ currents (L- and T-type), Na+ current, an hyperpolarization-activated current, three voltage-gated K+ currents, two Ca2+-activated K+ current, Ca2+-activated Cl current, non-specific cation current, Na+-Ca2+ exchanger, Na+-K+ pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular Ca2+ computed from known Ca2+ fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing [Ca2+]i. This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, [Ca2+]i and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical E-C coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels.
format	article
author	Wing-Chiu Tong Cecilia Y Choi Sanjay Kharche Arun V Holden Henggui Zhang Michael J Taggart
author_facet	Wing-Chiu Tong Cecilia Y Choi Sanjay Kharche Arun V Holden Henggui Zhang Michael J Taggart
author_sort	Wing-Chiu Tong
title	A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.
title_short	A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.
title_full	A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.
title_fullStr	A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.
title_full_unstemmed	A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.
title_sort	computational model of the ionic currents, ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/52d14292fc0746fdaad5e71a8e850025
work_keys_str_mv	AT wingchiutong acomputationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT ceciliaychoi acomputationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT sanjaykharche acomputationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT arunvholden acomputationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT hengguizhang acomputationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT michaeljtaggart acomputationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT wingchiutong computationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT ceciliaychoi computationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT sanjaykharche computationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT arunvholden computationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT hengguizhang computationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle AT michaeljtaggart computationalmodeloftheioniccurrentsca2dynamicsandactionpotentialsunderlyingcontractionofisolateduterinesmoothmuscle
_version_	1718424229082300416

A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.

Ejemplares similares