Simulation of ATP metabolism in cardiac excitation-contraction coupling.
To obtain insights into the mechanisms underlying the membrane excitation and contraction of cardiac myocytes, we developed a computer model of excitation-contraction coupling (Kyoto model: Jpn. J. Physiol. 53 (2003) 105). This model was further expanded by incorporating pivotal reactions of ATP metabolism; the model of mitochondrial oxidative phosphorylation by Korzeniewski and Zoladz (Biophys. Chem. 92 (2001) 17). The ATP-dependence of contraction, and creatine kinase and adenylate kinase were also incorporated. After minor modifications, the steady-state condition was well established for all the variables, including the membrane potential, contraction, and the ion and metabolite concentrations in sarcoplasmic reticulum, mitochondria and cytoplasm. Concentrations of major metabolites were close to the experimental data. Responses of the new model to anoxia were similar to experimental results of the P-31 NMR study in whole heart. This model serves as a prototype for developing a more comprehensive model of excitation-contraction-metabolism coupling.
Matsuoka
Satoshi
S
Department of Physiology and Biophysics, Kyoto University Graduate School of Medicine, Yoshida-Konoe, Sakyo-Ku, Kyoto, 606-8501, Japan. matsuoka@card.med.kyoto-u.ac.jp
Sarai
Nobuaki
N
Jo
Hikari
H
Noma
Akinori
A
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D003198:Computer Simulation; D003402:Creatine Kinase / Q000378:metabolism; D006329:Heart Conduction System / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D016276:Ventricular Function
D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D000263:Adenylate Kinase; D000254:Sodium-Potassium-Exchanging ATPase