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

Rong Tian, Jessica M. Halow, Markus Meyer, Wolfgang H. Dillmann, Vincent M. Figueredo, Joanne S. Ingwall, S. Albert Camacho

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

The free energy release from ATP hydrolysis (|ΔG(~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 |ΔG(~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 |ΔG~p| limits intracellular Ca2+ handling and thereby limits contractile reserve.

Original languageEnglish (US)
Pages (from-to)H2064-H2071
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume275
Issue number6 44-6
DOIs
StatePublished - Dec 1998

Keywords

  • Calcium ion
  • Creatine kinase
  • Free energy of adenosine 5'-triphosphate hydrolysis
  • Sarcoplasmic reticulum

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