System analysis of the effect of various drugs on cardiac contraction energetics.

Véronique Deschodt-Arsac, Guillaume Calmettes, Gilles Gouspillou, Richard Rouland, Eric Thiaudiere, Sylvain Miraux, Jean-Michel Franconi, Philippe Diolez

Résonance Magnétique des Systèmes Biologiques, UMR5536, Centre National de la Recherche Scientifique, Université Victor Segalen, Bordeaux 2, France.

Biochemical Society transactions 2010 Oct

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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).

Citation

Véronique Deschodt-Arsac, Guillaume Calmettes, Gilles Gouspillou, Richard Rouland, Eric Thiaudiere, Sylvain Miraux, Jean-Michel Franconi, Philippe Diolez. System analysis of the effect of various drugs on cardiac contraction energetics. Biochemical Society transactions. 2010 Oct;38(5):1319-21