Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528268
Title: A biophysically detailed mathematical model of a single late pregnant rat myometrial cell
Author: Choi, Cecilia
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2011
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Abstract:
While premature birth is still one of the major clinical problems worldwide, the exact physiological mechanisms underlying myometrium activity during pregnancy remain unclear. In this thesis, a novel biophysically detailed model was constructed using available experimental data to simulate chemical, electrical and mechanical activity in a late pregnant rat uterine myocycte. The developed model has been used to elucidate the ionic mechanism underlying myometrium functionality, providing better insights in the function of the uterus during pregnancy. The model consisted of 15 membrane currents, intracellular calcium handling process coupled with a sliding actin-myosin filament mechanical model to describe uterine behaviour and contractile activity at the single myocyte level. Each of the ionic currents were modelled using Hodgkin-Huxley-type equations. The simulated current traces and current-voltage curves were validated with experimental recordings and the model was further validated by the ability to produce a bursting action potential (AP) during an external stimulus. The model replicated the effects of estradiol during pregnancy, modulating the amplitude and activation properties of individual Ca2+ and K+ currents, therefore altering the AP configuration to a tonic-like plateau. The model also reproduced the actions of drugs to inhibit certain channels to investigate their roles in myometrium. Sensitivity analysis was performed to examine the model's behaviour to changing parameters. A simple 1-D study was conducted to investigate how electrical signals propagate along strand of cells. Although the model successfully replicated results similar to recordings seen in the experiments, limitations have to be addressed and more studies have to be carried out to further improve the model.
Supervisor: Zhang, Henggui Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.528268  DOI: Not available
Keywords: Uterus ; Modelling
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