TY - JOUR
T1 - Thermodynamic limitation for Ca2+ handling contributes to decreased contractile reserve in rat hearts
AU - Tian, Rong
AU - Halow, Jessica M.
AU - Meyer, Markus
AU - Dillmann, Wolfgang H.
AU - Figueredo, Vincent M.
AU - Ingwall, Joanne S.
AU - Camacho, S. Albert
PY - 1998/12
Y1 - 1998/12
N2 - 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.
AB - 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.
KW - Calcium ion
KW - Creatine kinase
KW - Free energy of adenosine 5'-triphosphate hydrolysis
KW - Sarcoplasmic reticulum
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U2 - 10.1152/ajpheart.1998.275.6.h2064
DO - 10.1152/ajpheart.1998.275.6.h2064
M3 - Article
C2 - 9843805
AN - SCOPUS:0032251466
SN - 0363-6135
VL - 275
SP - H2064-H2071
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6 44-6
ER -