Abstract
BackgroundThe 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.ResultsThe 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 (ΔGATPase). In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of ΔGATPase in the beating heart.ConclusionThe CK system stabilizes ΔGATPase by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.
Highlights
The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole
The following analyses demonstrate the importance of the creatine kinase (CK) system in stabilizing energetic states in the beating heart
The myoglobin concentration (CMb) is set to be a physiologically reasonable value 200 M [32], and the creatine kinase activity is set to be an arbitrary large value to ensure that the CK reaction is rapid enough to remain near equilibrium [33]
Summary
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-tobeat transient changes in blood flow and ATP hydrolysis rate. Myoglobin may work as an oxygen buffer [6,9], facilitate oxygen diffusion at low cellular oxygen tension [10,11,12], and/or catalyze chemical reactions (such as NO scavenging) [13,14,15]. In this study the buffering role of the CK system is investigated, and CK-facilitated diffusion of high-energy phosphate is not considered
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