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The Role of Calcium in the Energetics of Contracting Skeletal Muscle

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Summary

In its second messenger role in skeletal muscle, calcium coordinates the function of muscle (contractile activity) with its overall energetics, thereby controlling the provision of ATP in a time of need. Not only is ATP required for crossbridge turnover in the myofibrils, but it is also needed for the maintenance of ion pumps, nuclear activity, and so forth. When oxygen is limiting, the sustained contractions of both fast and slow muscle (after the immediate burst of activity) is primarily supported by glycogenolysis and the glycolytic pathway (anaerobic). Calcium is important to this process, and the compartmentation of the glycogen particle and some of the enzymes associated with the glycolytic pathway in the terminal cisternae of the sarcoplasmic reticulum ensures that the provision of glucose-6-phosphate to the glycolytic pathway for the generation of the needed ATP proceeds rapidly. The activation of phosphorylase and glycogenolysis by calcium-troponin-C is another example of the tight control of cellular energetics deemed possible by compartmentation within the cell. The regulation by calcium, therefore, is only dependent on the diffusion of calcium rather than diffusion of substrate.

When oxygen is not limiting (i.e. when a new steady-state is reached), the aerobic metabolism of pyruvate and fatty acids may be regulated in part by calcium at least in slow skeletal muscle. Oxidative phosphorylation, where ADP is phosphorylated to ATP, is thought to be controlled by the concentration of ADP in skeletal muscle. However, because of the obvious compartmentation of the mitochondria within the slow muscle fibre and the higher free calcium required for peak force development (5 µmol/L), the kinetics are theoretically favourable for the calcium cycle in slow muscle mitochondria to play an important role in the regulation of aerobic substrate oxidation, as it does in the heart. Although this hypothesis is attractive based on the available data, the direct demonstration of a major role for calcium as a regulator of substrate oxidation in slow muscle awaits experimentation.

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References

  • Armstrong RB, Phelps RO. Muscle fiber type composition of the rat hindlimb. American Journal of Anatomy 171: 259–272, 1984

    Article  PubMed  CAS  Google Scholar 

  • Baldwin KM, Reitman JS, Terjung RJ, Winder WW, Holloszy JO. Substrate depletion in different types of muscle and in liver during prolonged running. American Journal of Physiology 225: 1045–1050, 1973

    PubMed  CAS  Google Scholar 

  • Brandt N, Caswell A, Wen S-R, Talvenheimo J. Molecular interactions of the junctional foot protein and dihydropyridine receptor in skeletal triads. Journal of Membrane Biology 113: 237–251, 1990

    Article  PubMed  CAS  Google Scholar 

  • Carafoli E. The calcium cycle of mitochondria. FEBS Letters 104: 1–5, 1979

    Article  PubMed  CAS  Google Scholar 

  • Clausen T. The role of calcium in the activation of the glucose transport system. Cell Calcium 1: 311–325, 1980

    Article  CAS  Google Scholar 

  • Cohen P. Molecular mechanisms involved in the control of glycogenolysis in skeletal muscle by calcium ions and cyclic AMP. Biochemical Society Transactions 15(Suppl. 5): 999–1001, 1987

    PubMed  CAS  Google Scholar 

  • Donoso P, Hildago C. Sodium-calcium exchange in transverse tubules isolated from frog skeletal muscle. Biochimica et Biophysica Acta 978: 8–16, 1989

    Article  PubMed  CAS  Google Scholar 

  • Eisenberg BR. Adaptability of ultrastructure in the mammalian muscle. Journal of Experimental Biology 115: 55–68, 1985

    PubMed  CAS  Google Scholar 

  • Entman M, Keslensky S, Chu A, Van Winkle B. The sarcoplasmic reticulum-glycogenolytic complex in mammalian fast twitch skeletal muscle. Journal of Biological Chemistry 255(Suppl. 13): 6245–6252, 1980

    PubMed  CAS  Google Scholar 

  • Eusebi F, Miledi R, Takahashi T. Calcium transients in mammalian muscles. Nature 284: 560–561, 1980

    Article  PubMed  CAS  Google Scholar 

  • Fabiato A. Calcium-induced release of calcium from cardiac sarcoplasmic reticulum. American Journal of Physiology 245: C1–C14, 1983

    PubMed  CAS  Google Scholar 

  • Ferguson DG, Franzini-Armstrong C. The Ca2+ ATPase content of slow and fast twitch fibers of guinea pig. Muscle and Nerve 11: 561–570, 1988

    Article  PubMed  CAS  Google Scholar 

  • Franzini-Armstrong C, Ferguson DG, Champ C. Discrimination between fast- and slow-twitch fibres of guinea pig skeletal muscle using the relative surface density of junctional transverse tubule membrane. Journal of Muscle Research and Cell Motility 9: 403–414, 1988

    Article  PubMed  CAS  Google Scholar 

  • Fryer M, Neering I. Actions of caffeine on fast- and slow-twitch muscles of the rat. Journal of Physiology 416: 435–454, 1989

    PubMed  CAS  Google Scholar 

  • Garetto L, Carlsen R, Lee J-H, Walsh D. Calcium-dependent regulation of phosphorylase activation in a fast-twitch oxidative-glycol-ytic skeletal muscle. Molecular Pharmacology 33: 212–217, 1988

    PubMed  CAS  Google Scholar 

  • Goldstein M, Murphy D, Van Winkle B, Entman M. Cytochemical studies of a glycogen-sarcoplasmic reticulum complex. Journal of Muscle Research and Cell Motility 6: 177–187, 1985

    Article  PubMed  CAS  Google Scholar 

  • Hagg S, Taylor S, Ruderman N. Glucose metabolism in perfused skeletal muscle. Biochemical Journal 158: 203–210, 1976

    PubMed  CAS  Google Scholar 

  • Halestrap A. The regulation of the oxidation of fatty acids and other substrates in rat heart mitochondria by changes in the matrix volume induced by osmotic strength, valinomycin and Ca2+. Biochemical Journal 244: 159–164, 1987

    PubMed  CAS  Google Scholar 

  • Henriksen E, Rodnick K, Holloszy J. Activation of glucose transport in skeletal muscle by phospholipase C and phorbol ester. Journal of Biological Chemistry 234(Suppl. 36): 21536–21543, 1989

    Google Scholar 

  • Ingunn A, Singh B, Borrebaek B. The action of vasopressin and calcium on palmitate metabolism in hepatocytes and isolated mitochondria from rat liver. Archives of Biochemistry and Biophysics 222: 370–379, 1983

    Article  Google Scholar 

  • Kelso T, Hodgson D, Visscher A, Gollnick P. Some properties of different skeletal muscle fiber types: comparison of reference bases. Journal of Applied Physiology 62(Suppl. 4): 1436–1441, 1987

    PubMed  CAS  Google Scholar 

  • Keul J, Doll E, Keppler D. Energy metabolism of human muscle. Medicine and Sport 7: 9, 1972

    Google Scholar 

  • Klug G, Tibbits G. The effect of activity on calcium-mediated events in striated muscle. Exercise and Sport Science Reviews 16: 1–59, 1988

    Article  CAS  Google Scholar 

  • Krieger DA, Tate CA, McMillin-Wood J, Booth FW. Populations of rat skeletal muscle mitochondria after exercise and immobilization. Journal of Applied Physiology: Respiratory, Environment, Exercise Physiology 48: 23–28, 1980

    CAS  Google Scholar 

  • Lamb GD, Walsh T. Calcium currents, charge movement and dihydropyridine binding in fast- and slow-twitch muscles of rat and rabbit. Journal of Physiology (London) 393: 595–617, 1987

    CAS  Google Scholar 

  • Leberer E, Pette D. Immunochemical quantification of sarcoplasmic reticulum Ca-ATPase, of calsequestrin and of parvalbumin in rabbit skeletal muscles of defined fiber composition. European Journal of Biochemistry 156: 489–496, 1986

    Article  PubMed  CAS  Google Scholar 

  • McCormack J, Halestrap A, Denton R. The role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiological Reviews 70(Suppl. 2): 391–425, 1990

    PubMed  CAS  Google Scholar 

  • McMillin J, Madden M. The role of calcium in the control of respiration by muscle mitochondria. Medicine and Science in Sports and Exercise 21(Suppl. 4): 406–410, 1989

    PubMed  CAS  Google Scholar 

  • McMillin-Wood J, Wolkowicz PE, Chu A, Tate CA, Goldstein MA, et al. Calcium uptake by two preparations of mitochondria from heart. Biochimica et Biophysica Acta 591: 251–265, 1980

    Article  PubMed  CAS  Google Scholar 

  • Mickelson JR, Beaudry TM, Louis CF. Regulation of skeletal muscle sarcolemmal ATP-dependent calcium transport by calmodulin and cAMP-dependent protein kinase. Archives of Biochemistry and Biophysics 242: 127–136, 1985

    Article  PubMed  CAS  Google Scholar 

  • Mueckler M. Family of glucose-transporter genes: implications for glucose homeostasis and diabetes. Diabetes 39: 6–11, 1990

    Article  PubMed  CAS  Google Scholar 

  • Oscai L, Essig D, Palmer W. Lipase regulation of muscle triglyceride hydrolysis. Journal of Applied Physiology 69: 1571–1577, 1990

    PubMed  CAS  Google Scholar 

  • Perna A, Smogorzewski M, Massry S. Verapamil reverses PTH- or CRF-induced abnormal fatty acids oxidation in muscle. Kidney International 34: 774–778, 1988

    Article  PubMed  CAS  Google Scholar 

  • Rall J. Energetic aspects of skeletal muscle contraction: implications of fiber types. Exercise and Sport Sciences Reviews 13: 33–74, 1985

    PubMed  CAS  Google Scholar 

  • Rasmussen H. The calcium messenger system. New England Journal of Medicine 314: 1094–1100, 1986

    Article  PubMed  CAS  Google Scholar 

  • Rios E, Brum G. Involvement of dihydropyridine receptors in excitation-contraction coupling in skeletal muscle. Nature 325: 717–720, 1987

    Article  PubMed  CAS  Google Scholar 

  • Rossi A, Eppenberger H, Volpe P, Cotrufo R, Wallimann T. Muscle-type MM creatine kinase is specifically bound to sarcoplasmic reticulum and can support Ca2+ uptake and regulate local ATP/ADP ratios. Journal of Biological Chemistry 265(Suppl. 9): 5258–5266, 1990

    PubMed  CAS  Google Scholar 

  • Sembrowich WL, Quintinskie JJ, Li L. Calcium uptake in mitochondria from different skeletal muscle types. Journal of Applied Physiology 59: 137–141, 1985

    PubMed  CAS  Google Scholar 

  • Shoji S. The effect of the calcium ionophore A23187 on glucose uptake in slow and fast skeletal muscles of rats. Muscle and Nerve 13: 459–460, 1990

    PubMed  CAS  Google Scholar 

  • Siri LN, Sanchez JA, Stefani E. Effect of glycerol treatment on the calcium current of frog skeletal muscle. Journal of Physiology (London) 305: 87–96, 1980

    CAS  Google Scholar 

  • Somlyo AP, Somlyo AV. Electron probe analysis of calcium content and movements in sarcoplasmic reticulum, endoplasmic reticulum, mitochondria, and cytoplasm. Journal of Cardiovascular Pharmacology 8(Suppl. 8): S42–S47, 1986

    Article  PubMed  Google Scholar 

  • Stephenson DG, Williams DA. Calcium-activated force responses in fast- and slow-twitch skinned muscle fibres of the rat at different temperatures. Journal of Physiology (London) 317: 281–302, 1981

    CAS  Google Scholar 

  • Tate CA, Bonner HW, Leslie SW. Calcium uptake in skeletal muscle mitochondria: II. The effects of long-term chronic and acute exercise. European Journal of Applied Physiology and Occupational Physiology 39: 117–122, 1978

    Article  PubMed  CAS  Google Scholar 

  • Tejwani G. The role of phosphofructokinase in skeletal muscle contraction. Archives of Biological and Medical Experimentation 12: 617–628, 1979

    CAS  Google Scholar 

  • Van Winkle WB, Bick RJ, Tucker DE, Tate CA, Entman ML. Evidence for membrane microheterogeneity in the sarcoplasmic reticulum of fast twitch skeletal muscle. Journal of Biological Chemistry 257: 11689–11695, 1982

    PubMed  Google Scholar 

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Tate, C.A., Hyek, M.F. & Taffet, G.E. The Role of Calcium in the Energetics of Contracting Skeletal Muscle. Sports Med 12, 208–217 (1991). https://doi.org/10.2165/00007256-199112030-00005

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