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Am J Physiol Heart Circ Physiol 275: H2064-H2071, 1998;
0363-6135/98 $5.00
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Vol. 275, Issue 6, H2064-H2071, December 1998

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

Rong Tian1, Jessica M. Halow2, Markus Meyer3, Wolfgang H. Dillmann3, Vincent M. Figueredo2,4, Joanne S. Ingwall1, and S. Albert Camacho2,4

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 (|Delta G~p|) is decreased by inhibiting the creatine kinase (CK) reaction, which may limit the thermodynamic driving force for the sarcoplasmic reticulum (SR) Ca2+ pumps and thereby cause a decrease in contractile reserve. To determine whether a decrease in |Delta G~p| results in decreased contractile reserve by impairing Ca2+ handling, we measured left ventricular pressure and cytosolic Ca2+concentration ([Ca2+]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 Ca2+-ATPase activity, baseline left ventricular developed pressure, or baseline [Ca2+]c. When perfusate Ca2+ 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 [Ca2+]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 |Delta G~p| limits intracellular Ca2+ handling and thereby limits contractile reserve.

free energy of adenosine 5'-triphosphate hydrolysis; sarcoplasmic reticulum; creatine kinase; calcium ion


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