As part of the NIH funded Virtual Physiological Rat project (VPR) 1, we aim to simulate the integrated cardiovascular function of the rat, with the potential of providing new validated computer models that account for genetic variation across rat strains. Within the cardiovascular system we focus in particular on the heart, and the cardiac cell models of the ventricular myocyte. While there is a long history of significant advances in this field, in many cases the existing electrophysiology models have been derived combining different frameworks, resulting in the majority of currently applied models being parametrized from heterogeneous experimental sources. Thus, what is now required to further develop the field and increase the applicability of models to understanding wet lab contexts, is the development of species and temperature consistent models obtained by directly fitting parameters to experimental data. To address this issue we have implemented a rat electromechanical model by combining the electrophysiological framework of the Pandit 2001 2 model with the Hinch 2004 3 model of Ca2+ dynamics. To customize the coupled Pandit-Hinch model and automatically identify the parameters, we have implemented a linear regression parameter estimation method, following the approach of Sobie 2009 4. Synthetic data have been preliminarily used to generate simulated experimental data, physiological phenotypes have been quantified and a reverse regression has been performed to identify the parameter values specifying the previously generated simulations. The accuracy of the predictions is shown in (Fig. 1) in terms of R2 values for all the parameters used in the Hinch model using this approach. We were able to identify the majority of the parameters involved in the formulation of the sarcoplasmic reticulum Ca2+-ATPase (SERCA), the RyR channel and the L-type channel within tight ranges; predictions of parameters on the Na+/Ca2+ exchanger were less accurate. This approach will be applied to experimental data as part of the VPR project, with the potential of determing the choice of new experimental protocols according to parameterisation needs.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCB053
Poster Communications: Can we automatically identify parameters from experiments? Modeling calcium dynamics in the rat cardiac myocytes
S. Gattoni1, S. Niederer1, N. Smith1
1. Biomedical Engineering, King's College London, London, United Kingdom.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.