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Roles of the creatine kinase system and myoglobin in maintaining energetic state in the working heart.

Wu F, Beard DA - BMC Syst Biol (2009)

Bottom Line: The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole.In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of DeltaGATPase in the beating heart.The CK system stabilizes DeltaGATPase by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biotechnology and Bioengineering Center, Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. fwu@mcw.edu

ABSTRACT

Background: The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole. This study analyzes a previously developed model of cardiac energetics and oxygen transport to understand the roles of the creatine kinase system and myoglobin in maintaining the ATP hydrolysis potential during beat-to-beat transient changes in blood flow and ATP hydrolysis rate.

Results: The theoretical investigation demonstrates that elimination of myoglobin only slightly increases the predicted range of oscillation of cardiac oxygenation level during beat-to-beat transients in blood flow and ATP utilization. In silico elimination of myoglobin has almost no impact on the cytoplasmic ATP hydrolysis potential (DeltaGATPase). In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of DeltaGATPase in the beating heart.

Conclusion: The CK system stabilizes DeltaGATPase by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.

Show MeSH
Transient changes of myoglobin saturation, phosphate levels, cytoplasmic ATP hydrolysis potential, mitochondrial inner membrane potential, and mitochondrial ATP production rate in the heart without creatine kinase activity (no-CK). As for the control simulation of Figure 4, all variables are simulated for the time courses of the flow and ATP consumption rate in Figure 3.
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Figure 6: Transient changes of myoglobin saturation, phosphate levels, cytoplasmic ATP hydrolysis potential, mitochondrial inner membrane potential, and mitochondrial ATP production rate in the heart without creatine kinase activity (no-CK). As for the control simulation of Figure 4, all variables are simulated for the time courses of the flow and ATP consumption rate in Figure 3.

Mentions: To investigate the effects of CK buffering on the system, simulations of the no-CK system were performed using the same protocols used for the control, with the activity of creatine kinase is set to be zero for the simulations. Results illustrated in Figure 6 demonstrate the importance of the CK system in maintaining cardiac energetic state. Compared with the results in Figure 4, disabling the CK system causes considerably enhanced oscillations of SMb, [ATP]c, [Pi]c, [ADP]c, ΔGATPase, ΔΨ, and JANT during the cardiac cycle. In addition, removing CK prevents release of Pi from creatine phosphate (CrP) in response to increases in work rate. As a result, the average [Pi]c is reduced from ~2.1 mM in the normal system to ~0.7 mM in the no-CK system at the maximum workload.


Roles of the creatine kinase system and myoglobin in maintaining energetic state in the working heart.

Wu F, Beard DA - BMC Syst Biol (2009)

Transient changes of myoglobin saturation, phosphate levels, cytoplasmic ATP hydrolysis potential, mitochondrial inner membrane potential, and mitochondrial ATP production rate in the heart without creatine kinase activity (no-CK). As for the control simulation of Figure 4, all variables are simulated for the time courses of the flow and ATP consumption rate in Figure 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667476&req=5

Figure 6: Transient changes of myoglobin saturation, phosphate levels, cytoplasmic ATP hydrolysis potential, mitochondrial inner membrane potential, and mitochondrial ATP production rate in the heart without creatine kinase activity (no-CK). As for the control simulation of Figure 4, all variables are simulated for the time courses of the flow and ATP consumption rate in Figure 3.
Mentions: To investigate the effects of CK buffering on the system, simulations of the no-CK system were performed using the same protocols used for the control, with the activity of creatine kinase is set to be zero for the simulations. Results illustrated in Figure 6 demonstrate the importance of the CK system in maintaining cardiac energetic state. Compared with the results in Figure 4, disabling the CK system causes considerably enhanced oscillations of SMb, [ATP]c, [Pi]c, [ADP]c, ΔGATPase, ΔΨ, and JANT during the cardiac cycle. In addition, removing CK prevents release of Pi from creatine phosphate (CrP) in response to increases in work rate. As a result, the average [Pi]c is reduced from ~2.1 mM in the normal system to ~0.7 mM in the no-CK system at the maximum workload.

Bottom Line: The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole.In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of DeltaGATPase in the beating heart.The CK system stabilizes DeltaGATPase by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biotechnology and Bioengineering Center, Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. fwu@mcw.edu

ABSTRACT

Background: The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole. This study analyzes a previously developed model of cardiac energetics and oxygen transport to understand the roles of the creatine kinase system and myoglobin in maintaining the ATP hydrolysis potential during beat-to-beat transient changes in blood flow and ATP hydrolysis rate.

Results: The theoretical investigation demonstrates that elimination of myoglobin only slightly increases the predicted range of oscillation of cardiac oxygenation level during beat-to-beat transients in blood flow and ATP utilization. In silico elimination of myoglobin has almost no impact on the cytoplasmic ATP hydrolysis potential (DeltaGATPase). In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of DeltaGATPase in the beating heart.

Conclusion: The CK system stabilizes DeltaGATPase by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.

Show MeSH