A biophysically detailed mathematical model of a single late pregnant rat myometrial cell

Abstract

While premature birth is still one of the major clinical problems worldwide, theexact physiological mechanisms underlying myometrium activity during pregnancyremain unclear. In this thesis, a novel biophysically detailed model wasconstructed using available experimental data to simulate chemical, electrical andmechanical activity in a late pregnant rat uterine myocycte. The developed modelhas been used to elucidate the ionic mechanism underlying myometrium functionality,providing better insights in the function of the uterus during pregnancy. Themodel consisted of 15 membrane currents, intracellular calcium handling processcoupled with a sliding actin-myosin filament mechanical model to describe uterinebehaviour and contractile activity at the single myocyte level. Each of theionic currents were modelled using Hodgkin-Huxley-type equations. The simulatedcurrent traces and current-voltage curves were validated with experimentalrecordings and the model was further validated by the ability to produce a burstingaction potential (AP) during an external stimulus. The model replicated theeffects of estradiol during pregnancy, modulating the amplitude and activationproperties of individual Ca2+ and K+ currents, therefore altering the AP configurationto a tonic-like plateau. The model also reproduced the actions of drugsto inhibit certain channels to investigate their roles in myometrium. Sensitivityanalysis was performed to examine the model's behaviour to changing parameters.A simple 1-D study was conducted to investigate how electrical signals propagatealong strand of cells. Although the model successfully replicated results similarto recordings seen in the experiments, limitations have to be addressed and morestudies have to be carried out to further improve the model.

Date of Award	1 Aug 2011
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Henggui Zhang (Supervisor)