Calcified Tissue International

, Volume 96, Issue 3, pp 183–195 | Cite as

Skeletal Muscle: A Brief Review of Structure and Function

  • Walter R. FronteraEmail author
  • Julien Ochala


Skeletal muscle is one of the most dynamic and plastic tissues of the human body. In humans, skeletal muscle comprises approximately 40 % of total body weight and contains 50–75 % of all body proteins. In general, muscle mass depends on the balance between protein synthesis and degradation and both processes are sensitive to factors such as nutritional status, hormonal balance, physical activity/exercise, and injury or disease, among others. In this review, we discuss the various domains of muscle structure and function including its cytoskeletal architecture, excitation-contraction coupling, energy metabolism, and force and power generation. We will limit the discussion to human skeletal muscle and emphasize recent scientific literature on single muscle fibers.


Muscle actions Metabolism Force generation Exercise Sarcopenia Dystrophy 


Conflict of interest

Walter R. Frontera and Julien Ochala declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. 1.
    Wolfe RR (2006) The underappreciated role of muscle in health and disease. Am J Clin Nutr 84:475–482PubMedGoogle Scholar
  2. 2.
    Heymsfield SB, Adamek M, Gonzalez MC, Jia G, Thomas DM (2014) Assessing skeletal muscle mass: historical overview and state of the art. J Cachexia Sarcopenia Muscle 5:9–18CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Javan R, Horvath JJ, Case LE, Austin S, Corderi J, Dubrovsky A, Kishnani PS, Bashir MR (2013) Generating color-coded anatomic muscle maps for correlation of quantitative magnetic resonance imaging analysis with clinical examination in neuromuscular disorders. Muscle Nerve 48:293–295CrossRefPubMedGoogle Scholar
  4. 4.
    Fortin M, Videman T, Gibbons LE, Battié MC (2014) Paraspinal muscle morphology and composition: a 15-yr longitudinal magnetic resonance imaging study. Med Sci Sports Exerc 46:893–901CrossRefPubMedGoogle Scholar
  5. 5.
    Hikida RS (2011) Aging changes in satellite cells and their functions. Curr Aging Sci 4:279–297CrossRefPubMedGoogle Scholar
  6. 6.
    Wilkins JT, Krivickas LS, Goldstein R, Suh D, Frontera WR (2001) Contractile properties of adjacent segments of single human muscle fibers. Muscle Nerve 24:1319–1326CrossRefPubMedGoogle Scholar
  7. 7.
    Macaluso F, Myburgh KH (2012) Current evidence that exercise can increase the number of adult stem cells. J Muscle Res Cell Motil 33:187–198CrossRefPubMedGoogle Scholar
  8. 8.
    Bareja A, Holt JA, Luo G, Chang C, Lin J, Hinken AC, Freudenberg JM, Kraus WE, Evans WJ, Billin AN (2014) Human and mouse skeletal muscle stem cells: convergent and divergent mechanisms of myogenesis. PLoS ONE 9:e90398CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Thomas GD (2013) Functional muscle ischemia in Duchenne and Becker muscular dystrophy. Front Physiol 4:1–6CrossRefGoogle Scholar
  10. 10.
    Hoppeler H, Lüthi P, Claassen H, Weibel ER, Howald H (1973) The ultrastructure of the normal human skeletal muscle: a morphometric analysis of untrained men, women and well-trained orienteers. Pflügers Arch 344:217–232CrossRefPubMedGoogle Scholar
  11. 11.
    Gelfi C, Vasso M, Cerretelli P (2011) Diversity of human skeletal muscle in health and disease: contributions of proteomics. J Proteomics 74:774–795CrossRefPubMedGoogle Scholar
  12. 12.
    Greising SM, Gransee HM, Mantilla CB, Sieck GC (2012) Systems biology of skeletal muscle: fiber type as an organizing principle WIREs. Syst Biol Med 4:457–473Google Scholar
  13. 13.
    Ottenheijm CAC, Granzier H (2010) Lifting the nebula: novel insights into skeletal muscle contractility. Physiology 25:304–310CrossRefPubMedGoogle Scholar
  14. 14.
    Monroy JA, Powers KL, Gilomre LA, Uyeno TA, Lindstedt SL, Nishikawa KC (2012) What is the role of titin in active muscle? Exerc Sports Sci Rev 40:73–78CrossRefGoogle Scholar
  15. 15.
    Leonard TR, Herzog W (2010) Regulation of muscle force in the absence of actin–myosin-based cross-bridge interaction. Am J Physiol Cell Physiol 299:C14–C20CrossRefPubMedGoogle Scholar
  16. 16.
    Jayasinghe ID, Launikonis BS (2013) Three-dimensional reconstruction and analysis of the tubular system of vertebrate skeletal muscle. J Cell Sci 126:4048–4058CrossRefPubMedGoogle Scholar
  17. 17.
    Kerr JP, Ward CW, Bloch RJ (2014) Dysferlin at transverse tubules regulates Ca2+ homeostasis in skeletal muscle. Front Physiol 5. doi: 10.3389/fphys.2014.00089
  18. 18.
    Lamboley CR, Murphy RM, McKenna MJ, Lamb GD (2014) Sarcoplasmic reticulum Ca2+ uptake and leak properties, and SERCA isoform expression, in type I and type II fibres of human skeletal muscle. J Physiol 592:1381–1395CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Dahl R, Larsen S, Dohlmann TL, Qvortrup K, Helge JW, Dela F, Prats C (2014) Three dimensional reconstruction of the human skeletal muscle mitochondrial network as a tool to assess mitochondrial content and structural organization. Acta Physiol. doi: 10.1111/apha.12289
  20. 20.
    Yan Z, Lira VA, Greene NP (2012) Exercise training-induced regulation of mitochondrial quality. Exerc Sport Sci Rev 40:159–164PubMedCentralPubMedGoogle Scholar
  21. 21.
    Weisleder N, Brotto M, Komazaki S, Pan Z, Zhao X, Nosek T, Parness J, Takeshima H, Ma J (2006) Muscle aging is associated with compromised Ca2+ spark signalling and segregated intracellular Ca2+ release. J Cell Biol 174:639–645CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Liu G, Mac Gabhann F, Popel AS (2012) Effects of fiber type and size on the heterogeneity of oxygen distribution in exercising skeletal muscle. PLoS ONE 7(9):e44375. doi: 10.1371/journal.pone.0044375 CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Schiaffino S, Reggiani C (2011) Fiber types in mammalian skeletal muscles. Physiol Rev 91:1447–1531CrossRefPubMedGoogle Scholar
  24. 24.
    Galpin AJ, Raue U, Jemiolo B, Trappe TA, Harber MP, Minchev K, Trappe S (2012) Human skeletal muscle fiber type specific protein content. Anal Biochem 425:175–182CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    Bergström J (1962) Muscle electrolytes in man. Scand J Clin Lab Invest 14(Suppl):68Google Scholar
  26. 26.
    Larsson L, Moss RL (1993) Maximal velocity of unloaded shortening in relation to myosin heavy and light chain isoform composition in human skeletal muscles. J Physiol Lond 472:595–614CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Andersen JL (2003) Muscle fibre type adaptation in the elderly human muscle. Scand J Med Sci Sports 13:40–47CrossRefPubMedGoogle Scholar
  28. 28.
    Rebbeck RT, Karunasekara Y, Board PG, Beard NA, Casarotto MG, Dulhunty AF (2014) Skeletal muscle excitation–contraction coupling: who are the dancing partners? Int J Biochem Cell Biol 48:28–38CrossRefPubMedGoogle Scholar
  29. 29.
    Rayment I, Rypniewski WR, Schmidt-Base K, Smith R, Tomchick DR, Benning MM, Winkelmann DA, Wesenberg G, Holden HM (1993) Three-dimesnioanl structure of myosin sub-fragment-1: a molecular motor. Science 261:50–58CrossRefPubMedGoogle Scholar
  30. 30.
    Manring H, Abreu E, Brotto L, Weisleder N, Brotto M (2014) Novel excitation–contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases. Front Physiol. doi: 10.3389/fphys.2014.00037 PubMedCentralPubMedGoogle Scholar
  31. 31.
    Weibel ER (2013) The structural conditions for oxygen supply to muscle cells: the Krogh cylinder model. J Exp Biol 216(Pt 22):4135–4137CrossRefPubMedGoogle Scholar
  32. 32.
    Romjin JA, Coyle EF, Sidossi LS, Gastaldelli A, Horowitz JF, Endert E, Wolfe RR (1993) Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Physiol 265:E380–E391Google Scholar
  33. 33.
    Fulford J, Eston RG, Rowlands AV, Davies RC (2014) Assessment of magnetic resonance techniques to measure muscle damage 24 h after eccentric exercise. Scand J Med Sci Sports. doi: 10.1111/sms.12234
  34. 34.
    Huxley H, Niedergerke R (1954) Structural changes in muscle during contraction: interference microscopy of living muscle fibres. Nature 173:971–973CrossRefPubMedGoogle Scholar
  35. 35.
    Huxley H, Hanson J (1954) Changes in the cross-striations of muscle during contraction and stretch and their structural interpretation. Nature 173:973–976CrossRefPubMedGoogle Scholar
  36. 36.
    Larsson L, Moss RL (1993) Maximum velocity of shortening in relation to myosin isoform composition in single fibres from human skeletal muscles. J Physiol (Lond) 472:595–614CrossRefGoogle Scholar
  37. 37.
    Frontera WR, Krivickas L, Suh D, Hughes VA, Goldstein R, Roubenoff R (2000) Skeletal muscle fiber quality in older men and women. Am J Physiol 279:C611–C618Google Scholar
  38. 38.
    Li M, Larsson L (2010) Force-generating capacity of human myosin isoforms extracted from single muscle fibre segments. J Physiol 588:5105–5114CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Lamon S, Wallace MA, Russell AP (2014) The STARS signalling pathway: a key regulator of skeletal muscle function. Pflügers Arch. doi: 10.1007/s00424-014-1475-5
  40. 40.
    Seene T, Kaasik P, Alev K (2011) Muscle protein turnover in endurance training: a review. Int J Sports Med 32:905–911CrossRefPubMedGoogle Scholar
  41. 41.
    Green HJ, Balantyne CS, MacDougall JD, Tarnopolsky MA, Schertzer JD (2003) Adaptations in human sarcoplasmic reticulum to prolonged submaximal training. J Appl Physiol 94:2034–2042CrossRefPubMedGoogle Scholar
  42. 42.
    Russell AP (2010) Molecular regulation of skeletal muscle mass. Clin Exp Pharmacol Physiol 37:378–384CrossRefPubMedGoogle Scholar
  43. 43.
    Mayhew DL, Kim JS, Cross JM, Ferrando AA, Bamman MM (2009) Translational signalling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans. J Appl Physiol 107:1655–1662CrossRefPubMedCentralPubMedGoogle Scholar
  44. 44.
    Schiaffino S, Dyar KA, Ciciliot S, Blaauw B, Sandri M (2013) Mechanisms regulating skeletal muscle growth and atrophy. FEBS J 280:4294–4314CrossRefPubMedGoogle Scholar
  45. 45.
    Hitachi K, Tsuchida K (2014) Role of microRNAs in skeletal muscle hypertrophy. Front Physiol 4:1–7. doi: 10.3389/fphys.2013.00408 CrossRefGoogle Scholar
  46. 46.
    Blaauw B, Reggiani C (2014) The role of satellite cells in muscle hypertrophy. J Muscle Res Cell Motil 35:3–10CrossRefPubMedGoogle Scholar
  47. 47.
    Nader GA, von Walden F, Liu C, Lindvall J, Gutmann L, Pistilli EE, Gordon PM (2014) Resistance exercise training modulates acute gene expression during human skeletal muscle hypertrophy. J Appl Physiol 116:693–702CrossRefPubMedGoogle Scholar
  48. 48.
    Cermak NM, Res PT, de Groot LC, Saris WH, van Loon LJ (2012) Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta analysis. Am J Clin Nutr 96:1454–1464CrossRefPubMedGoogle Scholar
  49. 49.
    Rosenberg IH (1989) Summary comments. Am J Clin Nutr 50:1231–1233Google Scholar
  50. 50.
    Rosenberg IH (1997) Sarcopenia: origins and clinical relevance. J Nutr 127:990S–991SPubMedGoogle Scholar
  51. 51.
    Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M (2010) Sarcopenia: European consensus on definition and diagnosis. Age Ageing 39:412–423CrossRefPubMedCentralPubMedGoogle Scholar
  52. 52.
    Frontera WR, Hughes VA, Fielding RA, Fiatarone MA, Evans WJ, Roubenoff R (2000) Aging of skeletal muscle: a 12-yr longitudinal study. J Appl Physiol 88:1321–1326PubMedGoogle Scholar
  53. 53.
    Yamada M, Moriguch Y, Mitani T, Aoyama T, Arai H (2014) Age-dependent changes in skeletal muscle mass and visceral fat area in Japanese adults from 40 to 79 years-of-age. Geriatr Gerontol Int 14(Suppl 1):8–14CrossRefPubMedGoogle Scholar
  54. 54.
    Hughes VA, Frontera WR, Wood M, Evans WJ, Dallal GE, Roubenoff R, Fiatarone M (2001) Longitudinal muscle strength changes in older adults: influence of muscle mass, physical activity and health. J Gerontol (Biol Sci) 56A:B209–B217CrossRefGoogle Scholar
  55. 55.
    Reid KF, Pasha E, Doros G, Clark DJ, Patten C, Phillips EM, Widrick J, Frontera WR, Fielding RA (2014) Longitudinal decline of lower extremity muscle power in healthy and mobility-limited older adults: influence of muscle mass, strength, composition, neuromuscular activation and single fiber contractile properties. Eur J Appl Physiol 114:29–39CrossRefPubMedCentralPubMedGoogle Scholar
  56. 56.
    Verdijk LB, Koopman R, Schaart G, Meijer K, Savelberg HH, Dendale P, van Loon LJ (2007) Satellite cell content is specifically reduced in type II skeletal muscle fibers in elderly. Am J Physiol Endocrinol Metab 292:E151–E157CrossRefPubMedGoogle Scholar
  57. 57.
    McKay BR, Ogborn DI, Baker JM, Toth KG, Tarnopolsky MA, Parise G (2013) Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction. Am J Physiol Cell Physiol 304:C717–C728CrossRefPubMedCentralPubMedGoogle Scholar
  58. 58.
    Broskey NT, Greggio C, Boss A, Boutant M, Dwyer A, Schleuter L, Hans D, Gremion G, Kreis R, Boesch C, Canto C, Amati F (2014) Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training. J Clin Endocrinol Metab. doi: 10.1210/jc.2013-3983 PubMedGoogle Scholar
  59. 59.
    Miller MS, Toth MJ (2013) Myofilament protein alterations promote physical disability in aging and disease. Exerc Sport Sci Rev 41:93–99CrossRefPubMedCentralPubMedGoogle Scholar
  60. 60.
    D’Antona G, Pellegrino MA, Adami R, Rossi R, Carlizzi CN, Canepari M, Saltin B, Bottinelli R (2003) The effect of ageing and immobilization on structure and function of human skeletal muscle fibres. J Physiol 552:499–511CrossRefPubMedCentralPubMedGoogle Scholar
  61. 61.
    Moen RJ, Klein JC, Thomas DD (2014) Electron paramagnetic resonance resolves effects of oxidative stress on muscle proteins. Exerc Sport Sci Rev 42:30–36CrossRefPubMedCentralPubMedGoogle Scholar
  62. 62.
    Frontera WR, Reid KF, Phillips EM, Krivickas L, Hughes VA, Roubenoff R, Fielding RA (2008) Muscle fiber size and function in elderly humans: a longitudinal study. J Appl Physiol 105:637–642CrossRefPubMedCentralPubMedGoogle Scholar
  63. 63.
    Reid KF, Doros G, Clark DJ, Patten C, Carabello RJ, Cloutier GJ, Phillips EM, Krivickas LS, Frontera WR, Fielding RA (2012) Muscle power failure in mobility-limited older adults: preserved single fiber function despite lower whole muscle size, quality and neuromuscular activation. Eur J Appl Physiol 112:2289–2301CrossRefPubMedCentralPubMedGoogle Scholar
  64. 64.
    Ochala J, Frontera WR, Krivickas LS (2007) Single skeletal muscle fiber elastic and contractile characteristics in young and older men. J Gerontol Biol Sci 62A:375–381CrossRefGoogle Scholar
  65. 65.
    Monroy JA, Powers KL, Gilmore LA, Uyeno TA, Lindstedt SL, Nishikawa KC (2012) What is the role of titin in active muscle? Exerc Sport Sci Rev 40:73–78CrossRefPubMedGoogle Scholar
  66. 66.
    Ryu M, Jo J, Lee Y, Chung YS, Kim KM, Baek WC (2013) Association of physical activity with sarcopenia and sarcopenic obesity in community-dwelling older adults: the fourth Korea National health and nutrition examination survey. Age Ageing 42:734–740CrossRefPubMedGoogle Scholar
  67. 67.
    Bergouignan A, Rudwill F, Simon C, Blanc S (2011) Physical inactivity as the culprit of metabolic inflexibility: evidence from bed-rest studies. J Appl Physiol 111:1201–1210CrossRefPubMedGoogle Scholar
  68. 68.
    Trappe SW, Trappe TA, Lee GA, Widrick JJ, Costill DL, Fitts RH (2001) Comparison of a space shuttle flight (STS-78) and bed rest on human muscle function. J Appl Physiol 91:57–64PubMedGoogle Scholar
  69. 69.
    Alkner BA, Tesch PA (2004) Knee extensor and plantar flexor muscle size and function following 90 days of bed rest with or without resistance exercise. Eur J Appl Physiol 93:294–305CrossRefPubMedGoogle Scholar
  70. 70.
    Rittweger J, Möller K, Bareille MP, Felsenberg D, Zange J (2013) Muscle X-ray attenuation is not decreased during experimental bed rest. Muscle Nerve 47:722–730CrossRefPubMedGoogle Scholar
  71. 71.
    Trappe S, Trappe T, Gallagher P, Harber M, Alkner B, Tesch P (2004) Human single muscle fibre function with 84 day bed-rest and resistance exercise. J Physiol 557:501–513CrossRefPubMedCentralPubMedGoogle Scholar
  72. 72.
    Haus JM, Carrithers JA, Carroll CC, Tesch PA, Trappe TA (2007) Contractile and connective tissue protein content of human skeletal muscle: effects of 35 and 90 days of simulated microgravity and exercise countermeasures. Am J Physiol Regul Integr Comp Physiol 293:1722–1727CrossRefGoogle Scholar
  73. 73.
    Stevens L, Bastide B, Hedou J, Cieniewski-Bernard C, Montel V, Cochon L, Dupont E, Mounier Y (2013) Potential regulation of human muscle plasticity by MLC2 post-translational modifications during bed rest and countermeasures. Arch Biochem Biophys 540:125–132CrossRefPubMedGoogle Scholar
  74. 74.
    Collins J, Bonnemann CG (2010) Congenital muscular dystrophies: toward molecular therapeutic interventions. Curr Neurol Neurosci Rep 10:83–91CrossRefPubMedGoogle Scholar
  75. 75.
    Canepari M, Rossi R, Pansarasa O, Maffei M, Bottinelli R (2009) Actin sliding velocity on pure myosin isoforms from dystrophic mouse muscles. Muscle Nerve 40:249–256CrossRefPubMedGoogle Scholar
  76. 76.
    D’Antona G, Brocca L, Pansarasa O, Rinaldi R, Tupler R, Bottinelli R (2007) Structural and functional alterations of muscle fibres in the novel mouse model of facioscapulohumeral muscular dystrophy. J Physiol 584:997–1009CrossRefPubMedCentralPubMedGoogle Scholar
  77. 77.
    Krivickas LS, Ansved T, Suh D, Frontera WR (2000) Contractile properties of single muscle fibers in myotonic dystrophy. Muscle Nerve 23:529–537CrossRefPubMedGoogle Scholar
  78. 78.
    Ochala J (2008) Thin filament proteins mutations associated with skeletal myopathies: defective regulation of muscle contraction. J Mol Med 86:1197–1204CrossRefPubMedGoogle Scholar
  79. 79.
    Ochala J, Li M, Tajsharghi H, Kimber E, Tulinius M, Oldfors A, Larsson L (2007) Effects of a R133W beta-tropomyosin mutation on regulation of muscle contraction in single human muscle fibres. J Physiol Lond 581:1283–1292CrossRefPubMedCentralPubMedGoogle Scholar
  80. 80.
    Ochala J, Iwamoto H, Larsson L, Yagi N (2010) A myopathy-linked tropomyosin mutation severely alters thin filament conformational changes during activation. Proc Natl Acad Sci USA 107:9807–9812CrossRefPubMedCentralPubMedGoogle Scholar
  81. 81.
    Allen DL, Monke SR, Talmadge RJ, Roy RR, Edgerton VR (1995) Plasticity of myonuclear number in hypertrophied and atrophied mammalian skeletal muscle fibers. J Appl Physiol 78(5):1969–1976Google Scholar
  82. 82.
    Raven PB, Wasserman DH, Squires WG Jr, Muray TD (2013) Exercise physiology: an integrated approach. Wadsworth Cengage Learning, Belmont, CAGoogle Scholar
  83. 83.
    Sherwood L (2010) Human physiology. Brooks/Cole-Cengage Learning, Belmont, CAGoogle Scholar
  84. 84.
    Kenney WL, Wilmore JH, Costill DL (2012) Physiology of sport and exercise. Human Kinetics, Champaign, ILGoogle Scholar
  85. 85.
    Silverthorn U (2007) Human physiology. Pearson Education IncGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Physical Medicine and RehabilitationVanderbilt University School of MedicineNashvilleUSA
  2. 2.Department of PhysiologyUniversity of Puerto Rico School of MedicineSan JuanUSA
  3. 3.Department of Human and Aerospace Physiological SciencesKing’s College LondonLondonUK

Personalised recommendations