Incorporating Local Ca2+ Dynamics into Single Cell Ventricular Models

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 (Ca) dynamics regulate the excitationcontraction 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 Ca dynamics. In this paper we examine how we can improve existing ventricular cell models by replacing their description of Ca dynamics with the local Ca control models. When replacing the existing Ca dynamics in a given cell model with a different Ca description, the parameters of the Ca subsystem need to be refitted. 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 Ca dynamics into the ventricular single cell Noble 1998 model.