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Cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model

Calcium signalling plays a central role in regulating a wide variety of cell processes. A number of calcium signalling models exist in the literature that are capable of reproducing a variety of experimentally observed calcium transients. These models have been used to examine in more detail the mec...

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Autores principales: Appleby, Peter A., Shabir, Saqib, Southgate, Jennifer, Walker, Dawn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730703/
https://www.ncbi.nlm.nih.gov/pubmed/23864504
http://dx.doi.org/10.1098/rsif.2013.0487
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author Appleby, Peter A.
Shabir, Saqib
Southgate, Jennifer
Walker, Dawn
author_facet Appleby, Peter A.
Shabir, Saqib
Southgate, Jennifer
Walker, Dawn
author_sort Appleby, Peter A.
collection PubMed
description Calcium signalling plays a central role in regulating a wide variety of cell processes. A number of calcium signalling models exist in the literature that are capable of reproducing a variety of experimentally observed calcium transients. These models have been used to examine in more detail the mechanisms underlying calcium transients, but very rarely has a model been directly linked to a particular cell type and experimentally verified. It is important to show that this can be achieved within the general theoretical framework adopted by these models. Here, we develop a framework designed specifically for modelling cytosolic calcium transients in urothelial cells. Where possible, we draw upon existing calcium signalling models, integrating descriptions of components known to be important in this cell type from a number of studies in the literature. We then add descriptions of several additional pathways that play a specific role in urothelial cell signalling, including an explicit ionic influx term and an active pumping mechanism that drives the cytosolic calcium concentration to a target equilibrium. The resulting one-pool model of endoplasmic reticulum (ER)-dependent calcium signalling relates the cytosolic, extracellular and ER calcium concentrations and can generate a wide range of calcium transients, including spikes, bursts, oscillations and sustained elevations in the cytosolic calcium concentration. Using single-variate robustness and multivariate sensitivity analyses, we quantify how varying each of the parameters of the model leads to changes in key features of the calcium transient, such as initial peak amplitude and the frequency of bursting or spiking, and in the transitions between bursting- and plateau-dominated modes. We also show that, novel to our urothelial cell model, the ionic and purinergic P2Y pathways make distinct contributions to the calcium transient. We then validate the model using human bladder epithelial cells grown in monolayer cell culture and show that the model robustly captures the key features of the experimental data in a way that is not possible using more generic calcium models from the literature.
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spelling pubmed-37307032013-09-06 Cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model Appleby, Peter A. Shabir, Saqib Southgate, Jennifer Walker, Dawn J R Soc Interface Research Articles Calcium signalling plays a central role in regulating a wide variety of cell processes. A number of calcium signalling models exist in the literature that are capable of reproducing a variety of experimentally observed calcium transients. These models have been used to examine in more detail the mechanisms underlying calcium transients, but very rarely has a model been directly linked to a particular cell type and experimentally verified. It is important to show that this can be achieved within the general theoretical framework adopted by these models. Here, we develop a framework designed specifically for modelling cytosolic calcium transients in urothelial cells. Where possible, we draw upon existing calcium signalling models, integrating descriptions of components known to be important in this cell type from a number of studies in the literature. We then add descriptions of several additional pathways that play a specific role in urothelial cell signalling, including an explicit ionic influx term and an active pumping mechanism that drives the cytosolic calcium concentration to a target equilibrium. The resulting one-pool model of endoplasmic reticulum (ER)-dependent calcium signalling relates the cytosolic, extracellular and ER calcium concentrations and can generate a wide range of calcium transients, including spikes, bursts, oscillations and sustained elevations in the cytosolic calcium concentration. Using single-variate robustness and multivariate sensitivity analyses, we quantify how varying each of the parameters of the model leads to changes in key features of the calcium transient, such as initial peak amplitude and the frequency of bursting or spiking, and in the transitions between bursting- and plateau-dominated modes. We also show that, novel to our urothelial cell model, the ionic and purinergic P2Y pathways make distinct contributions to the calcium transient. We then validate the model using human bladder epithelial cells grown in monolayer cell culture and show that the model robustly captures the key features of the experimental data in a way that is not possible using more generic calcium models from the literature. The Royal Society 2013-09-06 /pmc/articles/PMC3730703/ /pubmed/23864504 http://dx.doi.org/10.1098/rsif.2013.0487 Text en http://creativecommons.org/licenses/by/3.0/ © 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research Articles
Appleby, Peter A.
Shabir, Saqib
Southgate, Jennifer
Walker, Dawn
Cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model
title Cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model
title_full Cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model
title_fullStr Cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model
title_full_unstemmed Cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model
title_short Cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model
title_sort cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730703/
https://www.ncbi.nlm.nih.gov/pubmed/23864504
http://dx.doi.org/10.1098/rsif.2013.0487
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