Abstract
The role of the hydrolysis products of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and inorganic phosphate (Pi), in the control of myocardial respiration was evaluated in vivo using 31P NMR. These studies were conducted to evaluate whether increases in the ATP hydrolysis products can be detected through the cardiac cycle or during increases in cardiac work. 31P NMR data acquisitions gated to various portions of the cardiac cycle (50 msec time resolution) revealed that cytosolic ATP, ADP and Pi did not change over the course of the cardiac cycle. These metabolites were also monitored during steady-state increases in cardiac work in conjunction with measurements of coronary blood flow and oxygen consumption. No changes were observed during 2 to 3 fold increases in myocardial oxygen consumption induced by various methods. These results demonstrate that the cytosolic ATP, ADP, and Pi concentrations remain relatively constant throughout the cardiac cycle and during physiological increases in cardiac work and oxygen consumption. Furthermore, it is shown that ADP and Pi cannot be solely responsible for the regulation of cardiac respiration in vivo based on the in vitro Km values of these compounds for oxidative phosphorylation. It is concluded that other mechanisms, working in concert with the simple kinetic feedback of ATP hydrolysis products, must be present in the cytosol to provide control of myocardial respiration in vivo.
Similar content being viewed by others
References
Gibbs CL, Chapman JB: Cardiac energetics. In: Handbook of Physiology. Cardiovascular System. Amer Physiol Soc, Bethesda MD, 1979, vol. 2, pp 775–804
Hassinen IE: Mitochondrial respiratory control in the myocardium. Biochem Biophys Acta 853: 135–151, 1986
Gibbs C: The cytoplasmic phosphorylation potential. Its possible role in the control of myocardial respiration and cardiac contractility. J Mol Cell Cardiol 17: 727–31, 1985
Chance B, Williams CM: The respiratory chain and oxidative phosphorylation. Adv Enzymol 17: 65–134, 1956
Jacobus WE, Moreadith RW, Vandegaer KM: Mitochondrial respiratory control: Evidence against the regulation of respiration by extramitochondrial phosphorylation potentials or by ATP/ADP ratios. J Biol Chem 257: 2397–2402, 1982
Erecinska M, Wilson DF: Regulation of cellular energy metabolism. J Memb Bio 70: 1–14, 1982
Meyer RA, Sweeney HL, Kushmerick MJ: A simple analysis of the ‘Phosphocreatine Shuttle’. Amer J Physiol 242: 1–11, 1982
Katz LA, Swain JA, Portman MA, Balaban RS: Intracellular pH and inorganic phosphate content of the heart in vivo: A 31P NMR study. Amer J Physiol 255: 11189–11196, 1988
Katz LA, Swain JA, Portman MA, Balaban RS: The relation between phosphate metabolites and oxygen consumption in the heart in vivo. Amer J Physiol 256: 14265–11274, 1989
Balaban RS, Kantor HL, Katz LA, Briggs RW: Relation between work and phosphate metabolites in the in vivo paced mammalian heart. Science 232: 1121–1123, 1986
Portman MA, Heineman FW, Balaban RS: Developmental changes in the relation between phosphate metabolites and oxygen consumption in the sheep heart in vivo. J Clin Invest 83: 456–464, 1989
Kantor HL, Briggs RW, Metz KR, Balaban RS: Gated in vivo examinations of cardiac metabolites with 31P NMR. Amer J Physiol 251: H171-H175, 1986
Taylor DJ, Styles P, Matthews PM, Arnold DA, Gadian DG, Bore P, Radda GK: Energetics of human muscle: Exercise induced ATP depletion. Magn Res Med 3: 44–54, 1986
Chance B, Leigh JS, Clark BJ, Maris J, Kent J, Nioka S, Smith D: Control of oxidative metabolism and oxygen delivery in human skeletal muscle: a steady-state analysis of the work/energy cost transfer function. Proc Natl Acad Sci 82: 8384–8388, 1985
From AHL, Petein MA, Michurski SP, Zimmer SD, Ugurbil K: 31-P-NMR studies of respiratory regulation on the intact myocardium. FEBS Let 206: 257–261, 1986
Snow TR, Kleinman LH, Lamanna JC, Wichsler AS, Jobsis FF: Response of cytochrome a, a3 in the in situ canine heart to transient ischemic episodes. Basic Res Cardiol 76: 289–304, 1981
Koretsky AP, Balaban RS: Changes in pyridine nucleotide levels alter oxygen consumption and extramitochondrial phosphates in isolated mitochondria: a 31P NMR and fluorescence study. Biochim Biophys Acta 893: 398–408, 1987
Balaban RS, Mandel LJ: Metabolic substrate utilization by rabbit proximal tubule. An NADH fluorescence study. Amer J Physiol 254: F407-F416, 1988
Denton RM, McCormick JG: On the role of the calcium transport cycle in heart and other mammalian mitochondria. FEBS Letters 119: 1–8, 1980
Katz LA, Koretsky AP, Balaban RS: A mechanism of respiratory control in the heart: a 31P NMR and NADH fluorescence study. FEBS Letters 221: 270–276, 1987
McCormick JG, England PJ: Ruthenium Red inhibits the activation of pyruvate dehydrogenase caused by inotropie agents in the perfused heart. Biochem J 214: 581–585, 1983
Katz LA, Koretsky AP, Balaban RS: The activation of dehydrogenase activity and cardiac respiration: A 31P NMR study. Amer J Physiol 255: H185-Hl88, 1988
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Balaban, R.S., Heineman, F.W. Control of mitochondrial respiration in the heart in vivo . Mol Cell Biochem 89, 191–197 (1989). https://doi.org/10.1007/BF00220775
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00220775