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

The free energy release from ATP hydrolysis (\Delta G(similar to 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(similar to 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 pmol 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(similar to p)/ limits intracellular Ca2+ handling and thereby limits contractile reserve.