Computational Modelling of Cardiac Metabolism in Atrial Myocytes

In this study, a computational model elucidating effects of cytosolic metabolic processes on cardiac metabolism and excitation-contraction coupling of an atrial cell is developed. Kinetic and thermodynamic rate laws were applied to describe Michaelis-Menten dynamics of metabolites in glycolysis and tricarboxylic acid cycle. Our computational model links cytosolic metabolism to mitochondrial metabolism by passive diffusion and carrier mediated transport using law of mass action, in adherence to the selective permeability of the mitochondrial membrane to metabolites. Simulation results for metabolic substrates in both compartments under control conditions showed stable dynamics for excitation-contraction coupling of the heart. Further simulation of dynamic modulated cardiac workload was consistent with experimental and theoretical expectations of substrate variation under different conditions. The ability of our model to simulate cardiac energy demand-supply balance under varied conditions confirms its strength which can help to further explore mechanisms of the pathology of disease resulted from metabolic dysfunction and discover the possibility of therapeutic intervention.