Skip to main content
SpringerLink
Log in

Functional coupling as a basic mechanism of feedback regulation of cardiac energy metabolism

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

In this review we analyze the concepts and the experimental data on the mechanisms of the regulation of energy metabolism in muscle cells. Muscular energetics is based on the force–length relationship, which in the whole heart is expressed as a Frank–Starling law, by which the alterations of left ventricle diastolic volume change linearly both the cardiac work and oxygen consumption. The second basic characteristics of the heart is the metabolic stability – almost constant levels of high energy phosphates, ATP and phosphocreatine, which are practically independent of the workload and the rate of oxygen consumption, in contrast to the fast-twitch skeletal muscle with no metabolic stability and rapid fatigue. Analysis of the literature shows that an increase in the rate of oxygen consumption by order of magnitude, due to Frank–Starling law, is observed without any significant changes in the intracellular calcium transients. Therefore, parallel activation of contraction and mitochondrial respiration by calcium ions may play only a minor role in regulation of respiration in the cells. The effective regulation of the respiration under the effect of Frank–Starling law and metabolic stability of the heart are explained by the mechanisms of functional coupling within supramolecular complexes in mitochondria, and at the subcellular level within the intracellular energetic units. Such a complex structural and functional organisation of heart energy metabolism can be described quantitatively by mathematical models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Nicholls D, Ferguson SJ: Bioenergetics. Academic Press, London, New York, 2002

    Google Scholar 

  2. Chance B, Williams GR: The respiratory chain and oxidative phosphorylation. Adv Enzymol 17: 65–134, 1956

    Google Scholar 

  3. Veech R, Lawson JWR, Cornell NW, Krebs H: Cytosolic phosphorylation potential. J Biol Chem 254: 6538–6547, 1979

    PubMed  Google Scholar 

  4. Connet RJ: Analysis of metabolic control: New insights using scaled creatine kinase model. Am J Physiol 254: R949–R959, 1988

    PubMed  Google Scholar 

  5. Aliev MK, Saks VA: Compartmentalised energy transfer in cardiomyocytes. Use of mathematical modeling for analysis of in vivo regulation of respiration. Biophys J 73: 428–445, 1997

    PubMed  Google Scholar 

  6. Saks VA, Aliev MK: Is there the creatine kinase equilibrium in working heart cells? Biochem Biophys Res Commun 227: 360–367, 1996

    Article  PubMed  Google Scholar 

  7. Kushmerick MJ, Meyer RA, Brown TB: Regulation of oxygen consumption in fast and slow-twitch muscle. Am J Physiol 263: C598–C606, 1992

    PubMed  Google Scholar 

  8. Neely JR, Denton RM, England PJ, Randle PJ: The effects of increased heart work on the tricarboxylate cycle and its interactions with glycolysis in the perfused rat heart. Biochem J 128: 147–159, 1972

    PubMed  Google Scholar 

  9. Neely JR, Liebermeister H, Battersby EJ, Morgan HE: Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol 212: 804–814, 1967

    PubMed  Google Scholar 

  10. Balaban RS, Kantor HL, Katz LA, Briggs RW: Relation between work and phosphate metabolite in the in vivo paced mammalian heart. Science 232: 1121–1123, 1986

    PubMed  Google Scholar 

  11. McCormack JG, Denton RM: The role of mitochondrial Ca2+ transport and matrix Ca2+ in signal transduction in mammalian tissues. Biochim Biophys Acta 1018: 287–291, 1990

    PubMed  Google Scholar 

  12. Korzeniewski B: Regulation of ATP supply during muscle contraction: Theoretical studies. Biochem J 330: 1189–1195, 1998

    PubMed  Google Scholar 

  13. Balaban RS: Cardiac energy metabolism homeostasis: Role of cytosolic calcium. J Mol Cell Cardiol 34: 1259–1271, 2002

    Article  PubMed  Google Scholar 

  14. Williamson JR, Ford C, Illingworth J, Safer B: Coordination of cyclic acid cycle activity with electron transport flux. Circ Res 38(suppl I): 39–51, 1976

    Google Scholar 

  15. Hansford RG: Relation between mitochondrial calcium transport and control of energy metabolism. Rev Physiol Biochem Pharmacol 102: 1–72, 1985

    PubMed  Google Scholar 

  16. Roberts V, Gurlini P, Tosello V, Nagai T, Miyawaki A, Di Lisa F, Pozzan T: Beat-to-beat oscillations of mitochondrial [Ca2+] in cardiac cells. EMBO J 17: 4998–5007, 2001

    Article  Google Scholar 

  17. Territo PR, Mootha VK, French SA, Balaban RS: Ca2+ activation of heart mitochondrial oxidative phosphorylation: Role of the F0/F1-ATPase. Am J Physiol 278: C423–C435, 2000

    PubMed  Google Scholar 

  18. Territo PR, French SA, Dunleavy MC, Evans FJ, Balaban RS: Calcium activation of heart mitochondrial oxidative phosphorylation. Rapid kinetics of mvO2, NADH and light scattering. J Biol Chem 276: 2586–1599, 2001

    Article  PubMed  Google Scholar 

  19. Starling EH, Visscher MB: The regulation of the energy output of the heart. J Physiol 62: 243–261, 1926

    Google Scholar 

  20. Mootha VK, Arai AE, Balaban RS: Maximum oxidative phosphorylation capacity of mammalian heart. Am J Physiol 272: H769–H775, 1997

    PubMed  Google Scholar 

  21. Wan B, Doumen C, Duszynski J, Salama G, Vary TC, Lanoue KF: Effects of cardiac work on electrical potential gradient across mitochondrial membrane in perfused rat hearts. Am J Physiol 265: H453–H460, 1993

    PubMed  Google Scholar 

  22. Saupe KW, Spindler M, Tian R, Ingwall JS: Impaired cardiac energetics in mice lacking muscle-specific isoenzymes of creatine kinase. Circ Res 82: 898–907, 1998

    PubMed  Google Scholar 

  23. Gustafson LA, Van Beek JH: Activation time of myocardial oxidative phosphorylation in creatine kinase and adenylate kinase knockout mice. Am J Physiol 282: H2259–H2264, 2002

    PubMed  Google Scholar 

  24. Bers D: Excitation-Contraction Coupling and Cardiac Contraction. Kluwer Academic Publishers, Dordrecht, 2001

    Google Scholar 

  25. Lipp P, Niggli E: Submicroscopic calcium signals as fundamental events of excitation-contraction coupling in guinea-pig cardiac myocytes. J Physiol 492: 31–38, 1996

    PubMed  Google Scholar 

  26. Niggli E: Localized intracellular calcium signalling: Calcium sparks and calcium quarks. Ann Rev Physiol 61: 311–335, 1999

    Article  Google Scholar 

  27. Gunter TE, Pfeifer DR: Mechanisms by which mitochondria transport calcium. Am J Physiol 258: C755–C786, 1990

    PubMed  Google Scholar 

  28. McCormack JG, Halestrap AP, Denton RM: Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev 70: 391–425, 1990

    PubMed  Google Scholar 

  29. Kentish JC, Wrzosek A: Changes in force and cytosolic Ca2+ concentration after length changes in isolated rat ventricular trabeculae. J Physiol 506: 431–444, 1998

    Article  PubMed  Google Scholar 

  30. Allen DG, Kentish JC: The cellular basis of the length-tension relation in cardiac muscle. J Mol Cell Cardiol 17: 821–840, 1985

    PubMed  Google Scholar 

  31. Shimizu J, Todaka K, Burkoff D: Load dependence of ventricular performance explained by model of calcium-myofilament interactions. Am J Physiol 282: H1081–H1091, 2002

    Google Scholar 

  32. Cornish-Bowden A: Fundamentals of enzyme kinetics. Portland Press, London, 1999, pp 1–343

    Google Scholar 

  33. Lakatta EG: Length modulation of muscle performance: Frank-Starling law of the heart. In: H.A. Fozzard, E. Haber, R.B. Jennings, A.M. Katz, H.E. Morgan (eds). The Heart and Cardiovascular System: Scientific Foundations. Raven Press, New York, 1991, pp 1325–1354

    Google Scholar 

  34. Opie LH: The Heart. Physiology, from Cell to Circulation (3rd ed). Lippincott-Raven Publishers, Philadelphia, PA, 1998, pp 43–63

    Google Scholar 

  35. Saks VA, Ventura-Clapier R (eds): Cellular Bioenergetics. Role of Coupled Creatine Kinase. Kluwer Academic Publishers, Dordrecht, Boston, 1994, pp 1–348

    Google Scholar 

  36. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger H: Transport of energy in muscle: The phosphoryl creatine shuttle. Biochem J 281: 21–40, 1992

    PubMed  Google Scholar 

  37. Wyss M, Kaddurah-Daouk R: Creatine and creatinine metabolism. Physiol Rev 80: 1107–1213, 2000

    PubMed  Google Scholar 

  38. Brandes R, Bers DM: Increased work in cardiac trabeculae causes decreased mitochondrial NADH fluorescence followed by slow recovery. Biophys J 71: 1024–1035, 1996

    PubMed  Google Scholar 

  39. Brandes R, Bers DM: Regulation of mitochondrial [NADH] by cytosolic [Ca2+] and work in trabeculae from hypertrophic and normal rat hearts. Circ Res 82: 1189–1198, 1998

    PubMed  Google Scholar 

  40. Brandes R, Bers DM: Analysis of the mechanisms of mitochondrial NADH regulation in cardiac trabeculae. Biophys J 77: 1666–1682, 1999

    PubMed  Google Scholar 

  41. Gibbs C: Respiratory control in normal and hypertrophic hearts. Cardiovasc Res 42: 567–570, 1999

    Article  PubMed  Google Scholar 

  42. Fiolet JWT, Braatscheer A, Schumacher CA: Intracellular [Ca2+] and vo2 after manipulation of the free energy of the Na+/Ca2+ exchanger in isolated rat ventricular myocytes. J Mol Cell Cardiol 27: 1513–1525, 1995

    Article  PubMed  Google Scholar 

  43. Khuchua Z, Belikova Y, Kuznetsov AV, Gellerich FN, Schild L, Neumann HW, Kunz WS: Caffeine and Ca2+ stimulate mitochondrial oxidative phosphorylation in saponin-skinned human skeletal muscle fibers due to activation of actomyosin ATPase. Biochim Biophys Acta 1188: 373–379, 1994

    PubMed  Google Scholar 

  44. Brown GC, Lakin-Thomas PL, Brand MD: Control of respiration and oxidative phosphorylation in isolated liver cells. Eur J Biochem 192: 355–362, 1990

    Article  PubMed  Google Scholar 

  45. Garlid K: Physiology of mitochondria. In: N. Sperelakis (ed). Cell Physiology Sourcebook. A Molecular Approach. Academic Press, New York, Boston, 2001, pp 139–151

    Google Scholar 

  46. Dzeja PP, Zeleznikar RJ, Goldberg ND: Adenylate kinase: Kinetic behaviour in intact cells indicates it is integral to multiple cellular processes. Mol Cell Biochem 184: 169–182, 1998

    Article  PubMed  Google Scholar 

  47. Dzeja PP, Vitkevicius KT, Redfield MM, Burnett JC, Terzik A: Adenylate-kinase catalyzed phosphotransfer in the myocardium: Increased contribution in heart failure. Circ Res 84: 1137–1143, 1999

    PubMed  Google Scholar 

  48. Kay L, Nicolay K, Wieringa B, Saks V, Wallimann T: Direct evidence of the control of mitochondrial respiration by mitochondrial creatine kinase in muscle cells in situ. J Biol Chem 275: 6967–6944, 2000

    Article  Google Scholar 

  49. Korge P: Factors limiting adenosine triphosphase function during high intensity exercise. Thermodynamic and regulatory considerations. Sports Med 20: 215–225, 1995

    PubMed  Google Scholar 

  50. Korzeniewski B, Zolade JA: A model of oxidative phosphorylation in mammalian skeletal muscle. Biophys Chem 92: 17–34, 2001

    PubMed  Google Scholar 

  51. Ishida Y, Riesinger I, Wallimann T, Paul RJ: Compartmentation of ATP synthesis and utilization in smooth muscle: Role of aerobic glycolysis and creatine kinase. Mol Cell Biochem 133/134: 39–50, 1994

    Article  Google Scholar 

  52. Ventura-Clapier R, Kuznetsov A, Veksler V, Boehm E, Anflous K: Functional coupling of creatine kinases in muscles: Species and tissue specificity. Mol Cell Biochem 184: 231–247, 1998

    Article  PubMed  Google Scholar 

  53. Saks VA, Chernousova GB, Gukovsky DE, Smirnov VN, Chazov EI: Studies of energy transport in heart cells. Mitochondrial isoenzyme of creatine phosphokinase: Kinetic properties and regulatory action of Mg2+ ions. Eur J Biochem 57: 273–290, 1975

    Article  PubMed  Google Scholar 

  54. Ogata T, Yamasaki Y: Ultra-high resolution scanning electron microscopy of mitochondria and sarcoplasmic reticulum arrangement in human red, white, and intermediate muscle fibers. Anatom Rec 248: 214–223, 1997

    Article  Google Scholar 

  55. Boudina S, Laclau MN, Tariosse L, Daret D, Gouverneur G, Boron-Adele S, Saks VA, Dos Santos P: Alteration of mitochondrial function in a model of chronic ischemia in vivo in rat heart. Am J Physiol 282: H821–H831, 2002

    Google Scholar 

  56. Schaper J, Meiser E, Stammler G: Ultrastructural morphometric analysis of myocardium from dogs, rats, hamsters, mice and from human hearts. Circ Res 56: 377–391, 1985

    PubMed  Google Scholar 

  57. Saks VA, Chernousova GB, Voronkov UI, Smirnov VN, Chazov EI: Study of energy transport mechanism in myocardial cells. Circ Res 34/35(suppl III), 138–149, 1974

    Google Scholar 

  58. Saks VA, Kaambre T, Sikk P, Eimre M, Orlova E, Paju K, Piirsoo A, Appaix F, Kay L, Regiz-Zagrosek V, Fleck E, Seppet E: Intracellular energetic units in red muscle cells. Biochem J 356: 643–657, 2001

    Article  PubMed  Google Scholar 

  59. Seppet E, Kaambre T, Sikk P, Tiivel T, Vija H, Kay L, Appaix F, Tonkonogi M, Sahlin K, Saks VA: Functional complexes of mitochondria with MgATPases of myofibrils and sarcoplasmic reticulum in muscle cells. Biochim Biophys Acta 1504: 379–395, 2001

    PubMed  Google Scholar 

  60. Appaix F, Kuznetsov A, Usson Y, Kay L, Andrienko T, Olivares J, Kaambre T, Sikk P, Margreiter R, Saks V: Possible role of cytoskeleton in intracellular arrangement and regulation of mitochondria. Exp Physiol 88: 175–190, 2003

    Article  PubMed  Google Scholar 

  61. Joubert F, Mazet JL, Mateo P, Joubert JA: 31P NMR detection of subcellular creatine kinase fluxes in the perfused rat heart: Contractility modifies energy transfer pathways. J Biol Chem 277: 18469–18476, 2002

    Article  PubMed  Google Scholar 

  62. Jacobus WE, Lehninger AL: Creatine kinase of rat mitochondria. Coupling of creatine phosphorylation to electron transport. J Biol Chem 248: 4803–4810, 1973

    PubMed  Google Scholar 

  63. Jacobus WE: Respiratory control and the integration of heart high-energy phosphate metabolism by mitochondrial creatine kinase. Ann Rev Physiol 47: 707–725, 1985

    Article  Google Scholar 

  64. Muller M, Moser R, Cheneval D, Carafoli E: Cardiolipin is the membrane receptor for mitochondrial creatine kinase. J Biol Chem 260: 3839–3843, 1985

    PubMed  Google Scholar 

  65. Barbour RL, Ribaudo J, Chan SHP: Effect of creatine kinase activity on mitochondrial ADP/ATP transport. Evidence for functional interaction. J Biol Chem 259: 8246–8251, 1984

    PubMed  Google Scholar 

  66. Kuznetsov AV, Saks VA: Affinity modification of creatine kinase and ATP-ADP translocase in heart mitochondria determination of their molar stoichiometry. Biochem Biophys Res Commun 134: 359–366, 1986

    Article  PubMed  Google Scholar 

  67. Saks VA, Khuchua ZA, Kuznetsov AV: Specific inhibition of ATP-ADP translocase in cardiac myoplasts by antibodies against mitochondrial creatine kinase. Biochim Biophys Acta. 891: 138–144, 1987

    PubMed  Google Scholar 

  68. Stachowiak O, Schlattner U, Dolder M, Wallimann T: Oligomeric state and membrane binding behaviour of creatine kinase isoenzymes: Implications for cellular function and mitochondrial structure. Mol Cell Biochem 184: 141–151, 1998

    Article  PubMed  Google Scholar 

  69. Saks VA, Chernousova GB, Gukovsky DE, Smirnov VN, EI Chazov: Studies of energy transport in heart cells. Mitochondrial isoenzyme of creatine phosphokinase: Kinetic properties and regulatory action of Mg2+ ions. Eur J Biochem 57: 273–290, 1975

    Article  PubMed  Google Scholar 

  70. Jacobus WE, Saks VA: Creatine kinase of heart mitochondria: Changes in its kinetic properties induced by coupling to oxidative phosphorylation. Arch Biochem Biophys 219: 167–178, 1982

    Article  PubMed  Google Scholar 

  71. Saks VA, Kuznetsov AV, Kupriyanov VV, Miceli MV, Jacobus WJ: Creatine kinase of rat heart mitochondria. The demonstration of functional coupling to oxidative phosphorylation in an inner membrane-matrix preparation. J Biol Chem 260: 7757–7764, 1985

    PubMed  Google Scholar 

  72. Saks VA, Khuchua ZA, Vasilyeva EV, Belikova YO, Kuznetsov A: Metabolic compartmentation and substrate channeling in muscle cells. Role of coupled creatine kinases in in vivo regulation of cellular respiration. A synthesis. Mol Cell Biochem 133/134: 155–192, 1994

    Article  Google Scholar 

  73. Fossel ET, Hoefeler H: A synthetic functional metabolic compartment. The role of propinquity in a linked pair of immobilized enzymes. Eur J Biochem 170: 165–171, 1987

    Article  PubMed  Google Scholar 

  74. Saks VA, Lipina NV, Smirnov VN, Chazov EI: Studies of energy transport in heart cells. The functional coupling between mitochondrial creatine phosphokinase and ATP-ADP translocase: Kinetic evidence. Arch Biochem Biophys 173: 34–41, 1976

    Article  PubMed  Google Scholar 

  75. Saks VA, Kupriyanov VV, Elizarova GV, Jacobus WE: Studies of energy transport in heart cells. The importance of creatine kinase localization for the coupling of mitochondrial phosphorylcreatine production to oxidative phosphorylation. J Biol Chem 255: 755–763, 1980

    PubMed  Google Scholar 

  76. Lipskaya T Yu: Mitochondrial creatine kinase: Properties and function. Biochemistry 66: 1098–1111, 2001

    PubMed  Google Scholar 

  77. Saks VA, Dos Santos P, Gellerich FN, Diolez P: Quantitative studies of enzyme-substrate compartmentation, functional coupling and metabolic channeling in muscle cells. Mol Cell Biochem 184: 291–307, 1998

    Article  PubMed  Google Scholar 

  78. Spindler M, Niebler R, Remkes H, Horn M, Lanz T, Neubauer S: Mitochondrial creatine kinase is critically necessary for normal myocardial high-energy phosphate metabolism. Am J Physiol 283: H680–H687, 2002

    Google Scholar 

  79. Kupriyanov VVV, Seppet EK, Emelin IV, Saks VA: Phosphocreatine production coupled to the glycolytic reaction in the cytosol of cardiac cells. Biochim Biophys Acta 592: 197–210, 1980

    PubMed  Google Scholar 

  80. Saks VA, Seppet EK, Lyulina NV: Comparative investigation of the role of creatine phosphokinase isoenzymes in energy metabolism of skeletal muscles and myocardium. Biokhimia 42: 579–588, 1977

    Google Scholar 

  81. Walsh B, Tonkonogi M, Soderlund K, Hultman E, Saks V, Sahlin K: The role of phosphorylcreatine and creatine in the regulation of mitochondrial respiration in human skeletal muscle. J Physiol 537: 971–978, 2001

    Article  PubMed  Google Scholar 

  82. Mahler M: First-order kinetics of muscle oxygen consumption, and an equivalent proportionality between QO2 and of phosphorylcreatine level. Implications for the control of respiration. J Gen Physiol 86: 135–165, 1985

    Article  PubMed  Google Scholar 

  83. Greenhaff PL: The creatine-phosphocreatine system: There's more than one song in its repertoire. J Physiol 537: 3, 2001

    Article  PubMed  Google Scholar 

  84. Hochachka PW, McClelland GB: Cellular metabolic homeostasis during large-scale ATP turnover in muscles. J Exp Biol 200: 381–386, 1997

    PubMed  Google Scholar 

  85. Weiss JN, Lamp ST: Cardiac ATP-sensitive K+ channels. Evidence for preferential regulation by glycolysis. J Gen Physiol 94: 911–935, 1989

    Article  PubMed  Google Scholar 

  86. Weiss JN, Korge P: The cytoplasm. No longer a well-mixed bag. Circ Res 89: 108–110, 2001

    PubMed  Google Scholar 

  87. Kummel L: Ca,MgATPase activity of permeabilized rat heart cells and its functional coupling to oxidative phosphorylation in the cells. Cardiovasc Res 22: 359–367, 1988

    PubMed  Google Scholar 

  88. Kaasik A, Veksler V, Boehm E, Novotova M, Minajeva A, Ventura-Clapier R: Energetic crosstalk between organelles. Architectural integration of energy production and utilization. Circ Res 89: 153–159, 2001

    PubMed  Google Scholar 

  89. Saks V, Kuznetsov AV, Andrienko T, Usson Y, Appaix F, Guerrero K, Kaambre T, Sikk P, Lemba M, Vendelin M: Heterogeneity of ADP diffusion and regulation of respiration in cardiac cells. Biophys J: 84: 3436–3456, 2003

    PubMed  Google Scholar 

  90. de Graaf RA, Van Kranenburg A, Nicolay K: In vivo 31P-NMR spectroscopy of ATP and phosphocreatine in rat skeletal muscle. Biophys J 78: 1657–1664, 2000

    PubMed  Google Scholar 

  91. Kinsey ST, Locke BR, Benke B, Moerland TS: Diffusional anisotropy is induced by subcellular barriers in skeletal muscle. NMR Biomed 12: 1–7, 1999

    Article  PubMed  Google Scholar 

  92. Collins TJ, Berridge MJ, Lipp P, Bootman MD: Mitochondria are morphologically and functionally heterogenous within cells. EMBO J 21: 1616–1627, 2002

    Article  PubMed  Google Scholar 

  93. Vendelin M, Kongas O, Saks VA: Regulation of mitochondrial respiration in heart cells analyzed by reaction-diffusion model of energy transfer. Am J Physiol Cell Physiol 278: C747–C764, 2000

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Structural and Quantitative Bioenergetics Research Group, Laboratory of Fundamental and Applied Bioenergetics, INSERM E0221, Joseph Fourier University, 2280 Rue de la Piscine, BP53–38041, Grenoble, Cedex 9, France

    V.A. Saks, M. Vendelin, K. Guerrero & L. Kay

  2. Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia

    V.A. Saks

  3. Department of Transplant Surgery, University Hospital Innsbruck, Innsbruck, Austria

    A.V. Kuznetsov

  4. Institute of Cybernetics, Tallinn, Estonia

    M. Vendelin

  5. Department of Pathophysiology, University of Tartu, Estonia

    E.K. Seppet

Authors
  1. V.A. Saks
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A.V. Kuznetsov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Vendelin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Guerrero
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. Kay
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E.K. Seppet
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saks, V., Kuznetsov, A., Vendelin, M. et al. Functional coupling as a basic mechanism of feedback regulation of cardiac energy metabolism. Mol Cell Biochem 256, 185–199 (2004). https://doi.org/10.1023/B:MCBI.0000009868.92189.fb

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:MCBI.0000009868.92189.fb

Search

Navigation