title: Cardiac system bioenergetics: metabolic basis of the Frank-Starling law.
abstract: The fundamental principle of cardiac behaviour is described by the Frank-Starling law relating force of contraction during systole with end-diastolic volume. While both work and respiration rates increase linearly with imposed load, the basis of mechano-energetic coupling in heart muscle has remained a long-standing enigma. Here, we highlight advances made in understanding of complex cellular and molecular mechanisms that orchestrate coupling of mitochondrial oxidative phosphorylation with ATP utilization for muscle contraction. Cardiac system bioenergetics critically depends on an interrelated metabolic infrastructure regulating mitochondrial respiration and energy fluxes throughout cellular compartments. The data reviewed indicate the significance of two interrelated systems regulating mitochondrial respiration and energy fluxes in cells: (1) the creatine kinase, adenylate kinase and glycolytic pathways that communicate flux changes generated by cellular ATPases within structurally organized enzymatic modules and networks; and (2) a secondary system based on mitochondrial participation in cellular calcium cycle, which adjusts substrate oxidation and energy-transducing processes to meet increasing cellular energy demands. By conveying energetic signals to metabolic sensors, coupled phosphotransfer reactions provide a high-fidelity regulation of the excitation-contraction cycle. Such integration of energetics with calcium signalling systems provides the basis for 'metabolic pacing', synchronizing the cellular electrical and mechanical activities with energy supply processes.
authors.affiliation: Structural and Quantitative Bioenergetics Research Group, Laboratory of Bioenergetics, Joseph Fourier University, 2280, Rue de la Piscine, BP53X -38041, Grenoble Cedex 9, France. valdur.saks@ujf-grenoble.fr
authors.forename: Valdur
authors.initials: V
authors.lastname: Saks
authors.forename: Petras
authors.initials: P
authors.lastname: Dzeja
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlattner
authors.forename: Marko
authors.initials: M
authors.lastname: Vendelin
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
authors.forename: Theo
authors.initials: T
authors.lastname: Wallimann
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D019069:Cell Respiration; D003402:Creatine Kinase / Q000502:physiology; D004734:Energy Metabolism; D006321:Heart / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D008929:Mitochondria, Heart / Q000378:metabolism*; D008954:Models, Biological; D009200:Myocardial Contraction; D010085:Oxidative Phosphorylation; D015398:Signal Transduction
chemical_list: D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D002118:Calcium