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Reference: Liren Li, (2011). Modelling of calcium handling in genetically modified mice. DPhil. University of Oxford.Citable link to this page:


Modelling of calcium handling in genetically modified mice

Abstract: This thesis develops biophysically-based data-driven mathematical models of intracellular calciumdynamics in ventricularmyocytes for both normal and genetically modified mouse hearts, based on species- and temperature-consistent experimental data. The models were subsequently applied to quantitatively examine the changes in calcium dynamics in mice with cardiomyocyte-specific knockout (KO) of the cardiac sarco/endoplasmic reticulum ATPase (SERCA2) gene, to determine the contributing mechanisms which underlie the ultimate development of heart failure in these animals. In Chapter 1, with emphasis on calcium dynamics and calcium regulation in heart failure, an overview of cardiac electrophysiology, excitation-contraction coupling and mathematical models of cardiac electrophysiology is provided. In Chapter 2, models of calcium dynamics in the ventricular myocytes from the C57BL/6 mouse heart at a physiological temperature is developed and validated based on species- and temperature-consistent measurements. In Chapter 3, the C57BL/6 model framework is re-parameterised to experimental data from the control and SERCA2 KO mice at 4 weeks after gene deletion. The models are then used to quantitatively characterise changes in calcium dynamics in the KO animals and the role of the compensatory mechanisms. In Chapter 4, the model framework is extended to include differential distributions of ion channels in the sarcolemma and the calcium dynamics in the sub-sarcolemmal space, with parameters in these sub-components fitted to experimentally measured calcium dynamics from the control and KO cardiomyocytes at 7-week after gene deletion. Finally in Chapter 5, conclusions are drawn, the limitations of this study are discussed, and the future extensions to this study are described.

Digital Origin:Born digital Type of Award:DPhil Level of Award:Doctoral Awarding Institution: University of Oxford


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 Bibliographic Details

Issue Date: 2011

Copyright Date: 2011 Identifiers

Urn: uuid:fa351516-9b3c-43c0-8bdc-5b0317cd5967 Item Description

Type: thesis;

Language: en Keywords: Calcium handling mathematical modelling cardiac electriphysiology genetically modified miceSubjects: Biology and other natural sciences (mathematics) Cardiovascular disease Biophysics Mathematical biology Tiny URL: ora:12283


Author: Dr Liren Li - institutionUniversity of Oxford facultyMathematical,Physical and Life Sciences Division - Computing Laboratory rese



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