Thermodynamic limitation for Ca2+ handling contributes to decreased contractile reserve in rat hearts

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 275; no. 6; p. H2064
• Main Authors: Tian, Rong, Halow, Jessica M, Meyer, Markus, Dillmann, Wolfgang H, Figueredo, Vincent M, Ingwall, Joanne S, Camacho, S. Albert
• Format: Journal Article
• Language: English
• Published: United States 01.12.1998
• Subjects: Animals; Calcium - metabolism; Calcium-Transporting ATPases - metabolism; Creatine Kinase - antagonists & inhibitors; Creatine Kinase - metabolism; Cytosol - metabolism; Enzyme Inhibitors - pharmacology; Iodoacetamide - pharmacology; Male; Myocardial Contraction - physiology; Osmolar Concentration; Perfusion; Pressure; Rats; Rats, Sprague-Dawley; Sarcoplasmic Reticulum - drug effects; Sarcoplasmic Reticulum - enzymology; Thermodynamics; Ventricular Function, Left - physiology
• ISSN: 0363-6135; 0002-9513; 1522-1539
• DOI: 10.1152/ajpheart.1998.275.6.H2064

1  Nuclear Magnetic Resonance Laboratory for Physiological Chemistry, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; 4  Division of Cardiology, Department of Medicine, San Francisco General Hospital, and 2  Department of Medicine, University of California, San Francisco 94110; and 3  Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California 92093 The free energy release from ATP hydrolysis (| G ~p |) is decreased by inhibiting the creatine kinase (CK) reaction, which may limit the thermodynamic driving force for the sarcoplasmic reticulum (SR) Ca 2+ pumps and thereby cause a decrease in contractile reserve. To determine whether a decrease in | G ~p | results in decreased contractile reserve by impairing Ca 2+ handling, we measured left ventricular pressure and cytosolic Ca 2+ concentration ([Ca 2+ ] c ; by indo 1 fluorescence) in isolated perfused rat hearts, with >95% inhibition of CK with 90 µmol iodoacetamide. Iodoacetamide did not directly alter SR Ca 2+ -ATPase activity, baseline left ventricular developed pressure, or baseline [Ca 2+ ] c . When perfusate Ca 2+ concentration was increased from 1.2 to 3.3 mM, LV developed pressure increased from 67 ± 6 to 119 ± 8 mmHg in control hearts ( P  < 0.05) but did not significantly increase in CK-inhibited hearts. Similarly, the amplitude of the [Ca 2+ ] c transient increased from 548 ± 54 to 852 ± 140 nM in control hearts ( P  < 0.05) but did not significantly increase in CK-inhibited hearts. We conclude that decreased | G ~p | limits intracellular Ca 2+ handling and thereby limits contractile reserve. free energy of adenosine 5'-triphosphate hydrolysis; sarcoplasmic reticulum; creatine kinase; calcium ion