Mathematical Modeling and Computer Simulation of ATP Metabolism in the Excitation-Contraction Coupling Phenomenon in the Rat Ventricular Myocyte

EasyChair Preprint no. 9015

Abstract

Several mathematical and computational models have already been developed to describe the complex process of cardiac excitation-contraction (EC) coupling. The model of Mullins & Bondarenko (2013) is cited as an example, which describes detailed mechanisms ranging from the function of individual ion channels to other important transporters, and satisfactorily simulates the characteristics of Action Potential (AP) and contraction in the mouse ventricular myocyte. However, the mathematical modeling did not include the equations of energy production and consumption used during the EC process, so it cannot be used to simulate possible problems in the production and consumption of ATP (Adenosine Triphosphate), the main source of energy for cells. In this context, the aim of the present paper is to present the implementation of the model describing ATP metabolism proposed by Cortassa et al. (2006) in the electromechanical model of Mullins & Bondarenko (2013). From this new mathematical model, and using the MATLAB platform, the EnergyECLab tool was developed. As an application of the tool, "in silico" experiments were performed to obtain the time course of ATP and phosphocreatine (CrP) concentration and, as well as, the inhibition of Ca2+-ATPase (SERCA) by Adenosine Diphosphate (ADP). The computational tool (EnergyECLab) developed to solve the system of Coupled Differential Equations (CDE's), has a friendly graphic interface and several didactic resources. As a result of the second "in silico" experiment, inhibition of SERCA by the ADP mechanism produced an increase in contraction force (30.7%) when compared to the control.

Keyphrases: ATP metabolism, Cardiac electrophysiology, mathematical modeling, Ventricular myocyte

@Booklet{EasyChair:9015,
  author = {Gabriel Motta and Matheus Camargo and Jefferson Mello and Daniel Goroso and Robson Silva},
  title = {Mathematical Modeling and Computer Simulation of ATP Metabolism in the Excitation-Contraction Coupling Phenomenon in the Rat Ventricular Myocyte},
  howpublished = {EasyChair Preprint no. 9015},

  year = {EasyChair, 2022}}