title: Mitochondrial calcium signaling and energy metabolism.
abstract: A computational model of energy metabolism in the mammalian ventricular myocyte is developed to study the effect of cytosolic calcium (Ca(2+)) transients on adenosine triphosphate (ATP) production. The model couples the Jafri-Dudycha model for tricarboxylic acid cycle regulation to a modified version of the Magnus-Keizer model for the mitochondria. The fluxes associated with Ca(2+) uptake and efflux (i.e., the Ca(2+) uniporter and Na(+)-Ca(2+) exchanger) and the F(1)F(0)-ATPase were modified to better model heart mitochondria. Simulations were performed at steady state and with Ca(2+) transients at various pacing frequencies generated by the Rice-Jafri-Winslow model for the guinea pig ventricular myocyte. The effects of the Ca(2+) transients for mitochondria both adjacent to the dyadic space and in the bulk myoplasm were studied. The model shows that Ca(2+) activation of both the tricarboxylic acid cycle and the F(1)F(0)-ATPase are necessary to produce increases in ATP production. The model also shows that in mitochondria located near the subspace, the large Ca(2+) transients can depolarize the mitochondrial membrane potential sufficiently to cause a transient decline in ATP production. However, this transient is of short duration, minimizing its impact on overall ATP production.
authors.affiliation: School of Computational Sciences, George Mason University, 10900 University Blvd., Occoquan Building, Room 328G, MSN 5B3, Manassas, VA 20110, USA.
authors.forename: My-Hanh T
authors.initials: MH
authors.lastname: Nguyen
authors.forename: M Saleet
authors.initials: MS
authors.lastname: Jafri
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D020013:Calcium Signaling / Q000502:physiology*; D003198:Computer Simulation; D004734:Energy Metabolism; D006352:Heart Ventricles / Q000166:cytology; D008929:Mitochondria, Heart / Q000378:metabolism*; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism*; D016276:Ventricular Function
chemical_list: D000255:Adenosine Triphosphate