System analysis of the effect of various drugs on cardiac contraction energetics.
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).
Deschodt-Arsac
Véronique
V
Résonance Magnétique des Systèmes Biologiques, UMR5536, Centre National de la Recherche Scientifique, Université Victor Segalen, Bordeaux 2, France.
Calmettes
Guillaume
G
Gouspillou
Gilles
G
Rouland
Richard
R
Thiaudiere
Eric
E
Miraux
Sylvain
S
Franconi
Jean-Michel
JM
Diolez
Philippe
P
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
D002317:Cardiovascular Agents; D010725:Phosphocreatine; D002118:Calcium; D004837:Epinephrine