Incorporating Local Ca2 + Dynamics into Single Cell Ventricular Models

Authors:
Anna Sher;David Abramson;Colin Enticott;Slavisa Garic;David Gavaghan;Denis Noble;Penelope Noble;Tom Peachey
Affiliations:
Comp. Biology Group, Oxford University Computing Laboratory, Oxford, UK OX1 3QD;Faculty of Information Technology, Monash University, Clayton, Victoria, Australia 3800;Faculty of Information Technology, Monash University, Clayton, Victoria, Australia 3800;Faculty of Information Technology, Monash University, Clayton, Victoria, Australia 3800;Comp. Biology Group, Oxford University Computing Laboratory, Oxford, UK OX1 3QD;Department of Physiology, Anatomy and Genetic, Oxford University, Oxford, UK OX1 3PT;Department of Physiology, Anatomy and Genetic, Oxford University, Oxford, UK OX1 3PT;Faculty of Information Technology, Monash University, Clayton, Victoria, Australia 3800
Venue:
ICCS '08 Proceedings of the 8th international conference on Computational Science, Part I
Year:
2008

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Abstract

Understanding physiological mechanisms underlying the activity of the heart is of great medical importance. Mathematical modeling and numerical simulation have become a widely accepted method of unraveling the underlying mechanism of the heart. Calcium (Ca2 +) dynamics regulate the excitation-contraction coupling in heart muscle cells and hence are among the key players in maintaining normal activity of the heart. Many existing ventricular single cell models lack the biophysically detailed description of the Ca2 +dynamics. In this paper we examine how we can improve existing ventricular cell models by replacing their description of Ca2 +dynamics with the local Ca2 +control models. When replacing the existing Ca2 +dynamics in a given cell model with a different Ca2 +description, the parameters of the Ca2 +subsystem need to be re-fitted. Moreover, the search through the plausible parameter space is computationally very intensive. Thus, the Grid enabled Nimrod/O software tools are used for optimizing the cell parameters. Nimrod/O provides a convenient, user-friendly framework for this as exemplified by the incorporation of local Ca2 +dynamics into the ventricular single cell Noble 1998 model.