title: System analysis of the effect of various drugs on cardiac contraction energetics.
abstract: We used MoCA (Modular Control and Regulation Analysis) to demonstrate in intact beating rat heart that physiological activation of contraction by adrenaline involves the almost perfect parallel activation of both mitochondria and myofibrils by intracellular Ca(2+). This explains the perfect homoeostasis of the energetic intermediate PCr (phosphocreatine) in heart. When using drugs specifically stimulating either supply or demand activities, MoCA helped reveal the very specific mode of regulation of heart contraction energetics. Only activation of myofibrils activity (demand), either by increasing intracellular Ca(2+) concentration or myofibrils sensitivity to Ca(2+), triggers activation of contractile activity. In contrast, the activation of mitochondrial activity (supply) has strictly no effect on contraction, either directly or through PCr changes (intermediate).
authors.affiliation: Résonance Magnétique des Systèmes Biologiques, UMR5536, Centre National de la Recherche Scientifique, Université Victor Segalen, Bordeaux 2, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Deschodt-Arsac
authors.forename: Guillaume
authors.initials: G
authors.lastname: Calmettes
authors.forename: Gilles
authors.initials: G
authors.lastname: Gouspillou
authors.forename: Richard
authors.initials: R
authors.lastname: Rouland
authors.forename: Eric
authors.initials: E
authors.lastname: Thiaudiere
authors.forename: Sylvain
authors.initials: S
authors.lastname: Miraux
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Franconi
authors.forename: Philippe
authors.initials: P
authors.lastname: Diolez
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D049490:Systems Biology
chemical_list: D002317:Cardiovascular Agents; D010725:Phosphocreatine; D002118:Calcium; D004837:Epinephrine