What is the lifespan of Skeletal Muscle Cells?

What is the lifespan of Skeletal Muscle Cells?

We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

I have read that skeletal muscle cells cannot multiply and are generally not created after early development. However, I have also read that they have a "lifespan" of 10-15 years. Could this lifespan actually be referring to the turnover rate of the majority of material in the cell, and that the literal lifespan of the cell (if we count all of its components, including the nucleus) would be the same as that of the owner?

Muscle cell

A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. [1] A skeletal muscle cell is long and threadlike with many nuclei and is called a muscle fiber. [1] Muscle cells (including myocytes and muscle fibers) develop from embryonic precursor cells called myoblasts. [2]

Myoblasts fuse to form multinucleated skeletal muscle cells known as syncytia in a process known as myogenesis. [3] [4] Skeletal muscle cells, and cardiac muscle cells contain myofibrils and sarcomeres and form a striated muscle tissue. [5]

Cardiac muscle cells form the cardiac muscle in the walls of the heart chambers, and have a single central nucleus. [6] Cardiac muscle cells are joined to neighboring cells by intercalated discs, and when joined together in a visible unit they are described as a cardiac muscle fiber. [7]

Smooth muscle cells control involuntary movements such as the peristalsis contractions in the esophagus and stomach. Smooth muscle has no myofibrils or sarcomeres and is therefore non-striated. Smooth muscle cells have a single nucleus.

There are well over 600 skeletal muscles in the human body, some of which are identified inFigure below. Skeletal muscles vary considerably in size, from tiny muscles inside the middle ear to very large muscles in the upper leg.

Skeletal Muscles. Skeletal muscles enable the body to move.

Structure of Skeletal Muscles

Each skeletal muscle consists of hundreds or even thousands of skeletal muscle fibers. The fibers are bundled together and wrapped in connective tissue, as shown Figure below. The connective tissue supports and protects the delicate muscle cells and allows them to withstand the forces of contraction. It also provides pathways for nerves and blood vessels to reach the muscles. Skeletal muscles work hard to move body parts. They need a rich blood supply to provide them with nutrients and oxygen and to carry away their wastes.

Skeletal Muscle Structure. A skeletal muscle contains bundles of muscle fibers inside a &ldquocoat&rdquo of connective tissue.

Skeletal Muscles and Bones

Skeletal muscles are attached to the skeleton by tough connective tissues called tendons(see Figure above). Many skeletal muscles are attached to the ends of bones that meet at a joint. The muscles span the joint and connect the bones. When the muscles contract, they pull on the bones, causing them to move.

Muscles can only contract. They cannot actively extend, or lengthen. Therefore, to move bones in opposite directions, pairs of muscles must work in opposition. For example, the biceps and triceps muscles of the upper arm work in opposition to bend and extend the arm at the elbow (see Figure below). What other body movements do you think require opposing muscle pairs?

Triceps and biceps muscles in the upper arm are opposing muscles.

Use It or Lose It

In exercises such as weight lifting, skeletal muscle contracts against a resisting force (see Figure below). Using skeletal muscle in this way increases its size and strength. In exercises such as running, the cardiac muscle contracts faster and the heart pumps more blood. Using cardiac muscle in this way increases its strength and efficiency. Continued exercise is necessary to maintain bigger, stronger muscles. If you don&rsquot use a muscle, it will get smaller and weaker&mdashso use it or lose it.

Myocyte Structure

Myocytes can be incredibly large, with diameters of up to 100 micrometers and lengths of up to 30 centimeters. The sarcoplasm is rich with glycogen and myoglobin, which store the glucose and oxygen required for energy generation, and is almost completely filled with myofibrils, the long fibers composed of
myofilaments that facilitate muscle contraction.

The sarcolemma of myocytes contains numerous invaginations (pits) called transverse tubules which are usually perpendicular to the length of the myocyte. Transverse tubules play an important role in supplying the myocyte with Ca + ions, which are key for muscle contraction.

Each myocyte contains multiple nuclei due to their derivation from multiple myoblasts, progenitor cells that give rise to myocytes. These myoblasts asre located to the periphery of the myocyte and flattened so
as not to impact myocyte contraction.

Figure (PageIndex<1>): Myocyte: Skeletal muscle cell: A skeletal muscle cell is surrounded by a plasma membrane called the sarcolemma with a cytoplasm called the sarcoplasm. A muscle fiber is composed of many myofibrils, packaged into orderly units.

Fiber- and Age-related Variation in Satellite Cell Frequency

Satellite cells were initially identified in frog leg muscles by electron microscopy [1], and subsequently have been identified in all higher vertebrates. In humans and mice, these quiescent [18], non-fibrillar, mononuclear cells are most plentiful at birth (estimated at 32% of sublaminar nuclei) [19]. The frequency declines post-natally, stabilizing to between 1 to 5% of skeletal muscle nuclei in adult mice [2]. Satellite cell frequency varies in different muscles, likely as a function of variation in fiber type composition (i.e. slow oxidative, fast oxidative, or fast glycolytic fibers). For example, the mouse soleus muscle, which is predominantly made up of slow oxidative fibers, has a higher number of satellite cells than the extensor digitorum longus (EDL) muscle, which primarily contains fast glycolytic fibers. Additionally, the absolute numbers of satellite cells increases in the soleus but not the EDL between 1 and 12 months of age, although the proportion of satellite cells decreases in both muscle types with increasing age [20]. In humans, the proportion of satellite cells in skeletal muscles also decreases with age, which may explain the decreased efficiency of muscle regeneration in older subjects [21]. Satellite cells from aged muscle also display reduced proliferative and fusion capacity, as well as a tendency to accumulate fat, all of which likely contribute to deteriorating regeneration capability [22, 23]. That endurance training can offset the decline in satellite cell number with age suggests that poorer regeneration is not simply a result of limited replicative potential of older satellite cells [24].


Buckingham, M. & Relaix, F. PAX3 and PAX7 as upstream regulators of myogenesis. Semin Cell Dev. Biol. 44, 115–125 (2015).

Relaix, F. & Zammit, P. S. Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage. Development 139, 2845–2856 (2012).

Relaix, F. et al. Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells. J. Cell Biol. 172, 91–102 (2006).

Der Vartanian, A. et al. PAX3 confers functional heterogeneity in skeletal muscle stem cell responses to environmental stress. Cell Stem Cell 24, 958–973 e959 (2019). Following TCDD exposure MuSCs respond heterogeneously based on their expression level of PAX3 which confers to MuSCs protection from differentiation and survival to environmental stress.

Machado, L. et al. In situ fixation redefines quiescence and early activation of skeletal muscle stem cells. Cell Rep. 21, 1982–1993 (2017). Quiescent muscle stem cells undergo major transcriptomic alterations during isolation. Fixing the tissue during isolation circumvents this problem, preserving the native, in vivo state of quiescence.

Pietrosemoli, N. et al. Comparison of multiple transcriptomes exposes unified and divergent features of quiescent and activated skeletal muscle stem cells. Skelet. Muscle 7, 28 (2017).

van den Brink, S. C. et al. Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations. Nat. Methods 14, 935–936 (2017).

van Velthoven, C. T. J. et al. Transcriptional profiling of quiescent muscle stem cells in vivo. Cell Rep. 21, 1994–2004 (2017).

Bjornson, C. R. et al. Notch signaling is necessary to maintain quiescence in adult muscle stem cells. Stem Cells 30, 232–242 (2012).

Mourikis, P. et al. A critical requirement for notch signaling in maintenance of the quiescent skeletal muscle stem cell state. Stem Cells 30, 243–252 (2012).

Baghdadi, M. B. et al. Notch-Induced miR-708 antagonizes satellite cell migration and maintains quiescence. Cell Stem Cell 23, 859–868 e855 (2018).

Wang, X. et al. KLF7 regulates satellite cell quiescence in response to extracellular signaling. Stem Cells 34, 1310–1320 (2016).

Mademtzoglou, D. et al. Cellular localization of the cell cycle inhibitor Cdkn1c controls growth arrest of adult skeletal muscle stem cells. Elife 7, (2018).

Griger, J. et al. Loss of Ptpn11 (Shp2) drives satellite cells into quiescence. Elife 6, (2017).

Wang, G. et al. p110alpha of PI3K is necessary and sufficient for quiescence exit in adult muscle satellite cells. EMBO J. 37, (2018).

Rion, N. et al. mTOR controls embryonic and adult myogenesis via mTORC1. Development (2019).

Rodgers, J. T. et al. mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert). Nature 510, 393–396 (2014).

Rodgers, J. T. et al. HGFA is an injury-regulated systemic factor that induces the transition of stem cells into GAlert. Cell Rep. 19, 479–486 (2017).

Lee, G. et al. Fully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to GAlert. Proc. Natl Acad. Sci. USA 115, E4463–E4472 (2018).

Scaramozza, A. et al. Lineage tracing reveals a subset of reserve muscle stem cells capable of clonal expansion under stress. Cell Stem Cell 24, 944–957.e5 (2019).

Tierney, M. T. & Sacco, A. Satellite cell heterogeneity in skeletal muscle homeostasis. Trends Cell Biol. 26, 434–444 (2016).

Webster, M. T. et al. Intravital imaging reveals ghost fibers as architectural units guiding myogenic progenitors during regeneration. Cell Stem Cell 18, 243–252 (2016).

Kuang, S. et al. Asymmetric self-renewal and commitment of satellite stem cells in muscle. Cell 129, 999–1010 (2007).

Chang, N. C. et al. The dystrophin glycoprotein complex regulates the epigenetic activation of muscle stem cell commitment. Cell Stem Cell 22, 755–768.e6 (2018).

Takaesu, G. et al. Activation of p38alpha/beta MAPK in myogenesis via binding of the scaffold protein JLP to the cell surface protein Cdo. J. Cell Biol. 175, 383–388 (2006).

Troy, A. et al. Coordination of satellite cell activation and self-renewal by Par-complex-dependent asymmetric activation of p38alpha/beta MAPK. Cell Stem Cell 11, 541–553 (2012).

Palacios, D. et al. TNF/p38α/polycomb signaling to Pax7 locus in satellite cells links inflammation to the epigenetic control of muscle regeneration. Cell Stem Cell 7, 455–469 (2010).

Perdiguero, E. et al. Genetic analysis of p38 MAP kinases in myogenesis: fundamental role of p38alpha in abrogating myoblast proliferation. EMBO J. 26, 1245–1256 (2007).

Crist, C. G. et al. Muscle satellite cells are primed for myogenesis but maintain quiescence with sequestration of Myf5 mRNA targeted by microRNA-31 in mRNP granules. Cell Stem Cell 11, 118–126 (2012).

Cheung, T. H. et al. Maintenance of muscle stem-cell quiescence by microRNA-489. Nature 482, 524–528 (2012).

Zismanov, V. et al. Phosphorylation of eIF2alpha is a translational control mechanism regulating muscle stem cell quiescence and self-renewal. Cell Stem Cell 18, 79–90 (2016).

Hausburg, M. A. et al. Post-transcriptional regulation of satellite cell quiescence by TTP-mediated mRNA decay. Elife 4, e03390 (2015).

Bye, A. J. H. et al. The RNA-binding proteins Zfp36l1 and Zfp36l2 act redundantly in myogenesis. Skelet. Muscle 8, 37 (2018).

de Morree, A. et al. Staufen1 inhibits MyoD translation to actively maintain muscle stem cell quiescence. Proc. Natl Acad. Sci. USA 114, E8996–E9005 (2017).

Kitajima, Y. et al. The Ubiquitin-Proteasome system is indispensable for the maintenance of muscle stem cells. Stem Cell Rep. 11, 1523–1538 (2018).

Tichy, E. D. et al. A robust Pax7EGFP mouse that enables the visualization of dynamic behaviors of muscle stem cells. Skelet. Muscle 8, 27 (2018).

Hosoyama, T. et al. Microgravity influences maintenance of the human muscle stem/progenitor cell pool. Biochem Biophys. Res. Commun. 493, 998–1003 (2017).

de Morree, A. et al. Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function. Science 366, 734–738 (2019).

Rocheteau, P. et al. A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division. Cell 148, 112–125 (2012).

Cho, D. S. & Doles, J. D. Single cell transcriptome analysis of muscle satellite cells reveals widespread transcriptional heterogeneity. Gene 636, 54–63 (2017).

Dell’Orso, S. et al. Single-cell analysis of adult skeletal muscle stem cells in homeostatic and regenerative conditions. Development 146, dev174177 (2019). This is the first largescale scRNA-seq analysis on MuSCs. Using up to 3081 freshly-isolated cells the study confirmed the large transcriptional heterogeneity of the MuSC pool both in homeostatic conditions and in the regenerative environment.

Porpiglia, E. et al. High-resolution myogenic lineage mapping by single-cell mass cytometry. Nat. Cell Biol. 19, 558–567 (2017).

Giordani, L. et al. High-dimensional single-cell cartography reveals novel skeletal muscle resident cell populations. Mol. Cell 74, 609–621.e6 (2019).

De Micheli A.J., F. P. et al. Single-cell analysis of the muscle stem cell hierarchy identifies heterotypic communication signals involved in skeletal muscle regeneration. Cell Rep. 30, 3583–3595.e5 (2020).

Hwang, A. B. & Brack, A. S. Muscle stem cells and aging. Curr. Top. Dev. Biol. 126, 299–322 (2018).

Tierney, M. T. et al. Muscle stem cells exhibit distinct clonal dynamics in response to tissue repair and homeostatic aging. Cell Stem Cell 22, 119–127 e113 (2018).

Rehman, J. Empowering self-renewal and differentiation: the role of mitochondria in stem cells. J. Mol. Med. 88, 981–986 (2010).

Martínez-Reyes, I. & Chandel, N. S. Mitochondrial TCA cycle metabolites control physiology and disease. Nat. Commun. 11, 102 (2020).

Ryall, J. G. The NAD(+)-dependent SIRT1 deacetylase translates a metabolic switch into regulatory epigenetics in skeletal muscle stem cells. Cell Stem Cell 16, 171–183 (2015).

Yucel, N. Glucose metabolism drives histone acetylation landscape transitions that dictate muscle stem cell function. Cell Rep. 27, 3939–3955 (2019).

Latil, M. et al. Skeletal muscle stem cells adopt a dormant cell state post mortem and retain regenerative capacity. Nat. Commun. 3, 903 (2012).

Pala, F. et al. Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis. J. Cell Sci. 131, jcs212977 (2018).

Cerletti, M. et al. Short-term calorie restriction enhances skeletal muscle stem cell function. Cell Stem Cell 10, 515–519 (2012).

Zhang, H. et al. NAD + repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352, 1436–1443 (2016).

Wellen, K. E. et al. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324, 1076–1080 (2009).

Shyh-Chang, N. & Ng, H.-H. The metabolic programming of stem cells. Genes Dev. 31, 336–346 (2017).

Pecqueur, C. et al. Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization. FASEB J. 22, 9–18 (2008).

L’honoré, A. et al. The role of Pitx2 and Pitx3 in muscle stem cells gives new insights into P38α MAP kinase and redox regulation of muscle regeneration. Elife 7, e32991 (2018). Metabolic regulation of redox state is crucial for MuSC activation and muscle regeneration.

Theret, M. et al. AMPKα1‐LDH pathway regulates muscle stem cell self‐renewal by controlling metabolic homeostasis. EMBO J. 36, 1946–1962 (2017).

Vander Heiden, M. G. et al. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029–1033 (2009).

Mashinchian, O. et al. The muscle stem cell niche in health and disease. Curr. Top. Dev. Biol. 126, 23–65 (2018).

Petrilli, L. L. et al. High-dimensional single-cell quantitative profiling of skeletal muscle cell population dynamics during regeneration. Cells 9, 1723 (2020).

Baghdadi, M. B. et al. Reciprocal signalling by Notch–Collagen V–CALCR retains muscle stem cells in their niche. Nature 557, 714 (2018).

Rayagiri, S. S. et al. Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal. Nat. Commun. 9, 1075 (2018).

Low, S. et al. Delta‐Like 4 activates notch 3 to regulate self‐renewal in skeletal muscle stem cells. Stem Cells 36, 458–466 (2018).

Goel, A. J. et al. Niche cadherins control the quiescence-to-activation transition in muscle stem cells. Cell Rep. 21, 2236–2250 (2017).

Eliazer, S. et al. Wnt4 from the niche controls the mechano-properties and quiescent state of muscle stem cells. Cell Stem Cell 25, 654–665.e4 (2019).

Christov, C. et al. Muscle satellite cells and endothelial cells: close neighbors and privileged partners. Mol. Biol. Cell 18, 1397–1409 (2007).

Verma, M. et al. Muscle satellite cell cross-talk with a vascular niche maintains quiescence via VEGF and notch signaling. Cell Stem Cell 23, 530–543.e539 (2018).

Latroche, C. et al. Coupling between myogenesis and angiogenesis during skeletal muscle regeneration is stimulated by restorative macrophages. Stem Cell Rep. 9, 2018–2033 (2017).

Sampath, S. C. et al. Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M. Nat. Commun. 9, 1531 (2018).

Kostallari, E. et al. Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence. Development 142, 1242–1253 (2015).

Arnold, L. et al. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J. Exp. Med. 204, 1057–1069 (2007).

Du, H. et al. Macrophage-released ADAMTS1 promotes muscle stem cell activation. Nat. Commun. 8, 669 (2017).

Varga, T. et al. Macrophage PPARγ, a lipid activated transcription factor controls the growth factor GDF3 and skeletal muscle regeneration. Immunity 45, 1038–1051 (2016).

Shang, M. et al. Macrophage-derived glutamine boosts satellite cells and muscle regeneration. Nature. 587, 626–631 (2020).

Scott, R. W. et al. Hic1 defines quiescent mesenchymal progenitor subpopulations with distinct functions and fates in skeletal muscle regeneration. Cell Stem Cell 25, 797–813 (2019).

Malecova, B. et al. Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy. Nat. Commun. 9, 3670 (2018).

Lukjanenko, L. et al. Aging disrupts muscle stem cell function by impairing matricellular WISP1 secretion from fibro-adipogenic progenitors. Cell Stem Cell 24, 433–446 (2019). FAPs secrete WISP1 during muscle injury to promote asymmetric division of satellite cells.

Wosczyna, M. N. et al. Mesenchymal stromal cells are required for regeneration and homeostatic maintenance of skeletal muscle. Cell Rep. 27, 2029–2035 (2019).

Lemos, D. R. et al. Nilotinib reduces muscle fibrosis in chronic muscle injury by promoting TNF-mediated apoptosis of fibro/adipogenic progenitors. Nat. Med. 21, 786–794 (2015).

Morgan, J. E. et al. Necroptosis mediates myofibre death in dystrophin-deficient mice. Nat. Commun. 9, 3655 (2018).

Sreenivasan, K. et al. Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles. Cell Rep. 31, 107652 (2020).

Zhou, S. et al. Myofiber necroptosis promotes muscle stem cell proliferation via releasing Tenascin-C during regeneration. Cell. Res. 30, 1063–1077 (2020).

Juban, G. et al. AMPK activation regulates LTBP4-dependent TGF-beta1 secretion by pro-inflammatory macrophages and controls fibrosis in Duchenne Muscular Dystrophy. Cell Rep. 25, 2163–2176 e2166 (2018).

Ito, N. et al. Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells. Sci. Rep. 7, 8097 (2017).

Bar-Nur, O. et al. Direct reprogramming of mouse fibroblasts into functional skeletal muscle progenitors. Stem Cell Rep. 10, 1505–1521 (2018).

Dumont, N. A. & Rudnicki, M. A. Targeting muscle stem cell intrinsic defects to treat Duchenne muscular dystrophy. NPJ Regen. Med. 1, (2016).

Wang, Y. X. et al. EGFR-Aurka signaling rescues polarity and regeneration defects in dystrophin-deficient muscle stem cells by increasing asymmetric divisions. Cell Stem Cell 24, 419–432 e416 (2019).

Boldrin, L. et al. Satellite cells from dystrophic muscle retain regenerative capacity. Stem Cell Res 14, 20–29 (2015).

Muntoni, F. et al. Muscular weaknes in the mdx mouse. J. Neurol. Sci. 120, 71–77 (1993).

Grounds, M. D. et al. Towards developing standard operating procedures for pre-clinical testing in the mdx mouse model of Duchenne Muscular Dystrophy. Neurobiol. Dis. 31, 1–19 (2008).

Boscolo Sesillo, F. et al. Muscle stem cells give rise to rhabdomyosarcomas in a severe mouse model of Duchenne Muscular Dystrophy. Cell Rep. 26, 689–701 e686 (2019).

Chan, S. S. et al. Skeletal muscle stem cells from PSC-derived teratomas have functional regenerative capacity. Cell Stem Cell 23, 74–85 e76 (2018).

Lukjanenko, L. et al. Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice. Nat. Med. 22, 897–905 (2016).

Bentzinger, C. F. et al. Fibronectin regulates Wnt7a signaling and satellite cell expansion. Cell Stem Cell 12, 75–87 (2013).

Liu, L. et al. Impaired Notch signaling leads to a decrease in p53 activity and mitotic catastrophe in aged muscle stem cells. Cell Stem Cell 23, 544–556.e544 (2018).

White, J. P. et al. The AMPK/p27Kip1 axis regulates autophagy/apoptosis decisions in aged skeletal muscle stem cells. Stem Cell Rep. 11, 425–439 (2018).

Solanas, G. et al. Aged stem cells reprogram their daily rhythmic functions to adapt to stress. Cell 170, 678–692.e620 (2017). The oscillating transcriptome in stem cells is reprogrammed with aging, switching from homeostasis-related to tissue-specific stress genes. Long-term caloric restriction can prevent the reprogramming of aged stem cells.

Boldrin, L. et al. The effect of calorie restriction on mouse skeletal muscle is sex, strain and time-dependent. Sci. Rep. 7, 5160 (2017).

Dos Santos, M. Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers. Nat. Commun. 11, 5102 (2020).

Kim, M. et al. Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells. Nat. Commun. 11, 6375 (2020).

Chemello, F. et al. Degenerative and regenerative pathways underlying Duchenne muscular dystrophy revealed by single-nucleus RNA sequencing. Proc. Natl Acad. Sci. USA. 117, 29691–29701 (2020).

del Sol, A. et al. Computational strategies for niche-dependent cell conversion to assist stem cell therapy. Trends Biotechnol. 37, 687–696 (2019).

What is the lifespan of Skeletal Muscle Cells? - Biology

A subscription to J o VE is required to view this content. You will only be able to see the first 20 seconds .

The JoVE video player is compatible with HTML5 and Adobe Flash. Older browsers that do not support HTML5 and the H.264 video codec will still use a Flash-based video player. We recommend downloading the newest version of Flash here, but we support all versions 10 and above.

If that doesn't help, please let us know.

Skeletal muscles, striated tissues under the voluntary control of the somatic nervous system, are attached to bones through collagenous fibers called tendons. They are enclosed in a connective tissue called epimysium, which distinguishes the muscle from surrounding structures.

Within each skeletal muscle, like the biceps brachii, are numerous cell bundles, called fascicles, that are also surrounded by connective fascia, perimysium. Each fascicle contains multiple muscle cells, which are individually-enclosed in a plasma membrane known as the sarcolemma. A single muscle cell can be further broken down into myofibrils, filaments composed of actin and mysosin, the functional unit referred to as the sarcomere.

20.5: Skeletal Muscle Anatomy

Skeletal muscle is the most abundant type of muscle in the body. Tendons are the connective tissue that attaches skeletal muscle to bones. Skeletal muscles pull on tendons, which in turn pull on bones to carry out voluntary movements.

Skeletal muscles are surrounded by a layer of connective tissue called epimysium, which helps protect the muscle. Beneath the epimysium, an additional layer of connective tissue, called perimysium, surrounds and groups together subunits of skeletal muscle called fasciculi.

Each fascicle is a bundle of skeletal muscle cells, or myocytes, which are often called skeletal muscle fibers due to their size and cylindrical appearance. Between the muscle fibers is an additional layer of connective tissue called endomysium.

The muscle fiber membrane is called the sarcolemma. Each muscle fiber is made up of multiple rod-like chains called myofibrils, which extend across the length of the muscle fiber and contract. Myofibrils contain subunits called sarcomeres, which are made up of actin and myosin in thin and thick filaments, respectively.

Actin contains myosin-binding sites that allow thin and thick filaments to connect, forming cross bridges. For a muscle to contract, accessory proteins that cover myosin-binding sites on thin filaments must be displaced to enable the formation of cross bridges. During muscle contraction, cross bridges are repeatedly broken and formed at binding sites further along the actin.

Rall, Jack A. &ldquoGeneration of Life in a Test Tube: Albert Szent-Gyorgyi, Bruno Straub, and the Discovery of Actin.&rdquo Advances in Physiology Education 42, no. 2 (April 20, 2018): 277&ndash88. [Source]


Figure 2. Smooth muscle cells do not have striations, while skeletal muscle cells do. Cardiac muscle cells have striations, but, unlike the multinucleate skeletal cells, they have only one nucleus. Cardiac muscle tissue also has intercalated discs, specialized regions running along the plasma membrane that join adjacent cardiac muscle cells and assist in passing an electrical impulse from cell to cell.

  • Smooth muscle or “involuntary muscle” consists of spindle shaped muscle cells found within the walls of organs and structures such as the esophagus, stomach, intestines, bronchi, uterus, ureters, bladder, and blood vessels. Smooth muscle cells contain only one nucleus and no striations.
  • Cardiac muscle is also an “involuntary muscle” but it is striated in structure and appearance. Like smooth muscle, cardiac muscle cells contain only one nucleus. Cardiac muscle is found only within the heart.
  • Skeletal muscle or “voluntary muscle” is anchored by tendons to the bone and is used to effect skeletal movement such as locomotion. Skeletal muscle cells are multinucleated with the nuclei peripherally located. Skeletal muscle is called ‘striated’ because of the longitudinally striped appearance under light microscopy. Functions of the skeletal muscle include:
    • Support of the body
    • Aids in bone movement
    • Helps maintain a constant temperature throughout the body
    • Assists with the movement of cardiovascular and lymphatic vessels through contractions
    • Protection of internal organs and contributing to joint stability

    Cardiac and skeletal muscle are striated in that they contain sarcomeres and are packed into highly-regular arrangements of bundles smooth muscle has neither. Striated muscle is often used in short, intense bursts, whereas smooth muscle sustains longer or even near-permanent contractions.

    Skeletal muscle is further divided into several subtypes:

    1. Type I, slow oxidative, slow twitch, or “red” muscle is dense with capillaries and is rich in mitochondria and myoglobin, giving the muscle tissue its characteristic red color. It can carry more oxygen and sustain aerobic activity.
    2. Type II, fast twitch, muscle has three major kinds that are, in order of increasing contractile speed:
      1. Type IIa, which, like slow muscle, is aerobic, rich in mitochondria and capillaries and appears red.
      2. Type IIx (also known as type IId), which is less dense in mitochondria and myoglobin. This is the fastest muscle type in humans. It can contract more quickly and with a greater amount of force than oxidative muscle, but can sustain only short, anaerobic bursts of activity before muscle contraction becomes painful (often attributed to a build-up of lactic acid). N.B. in some books and articles this muscle in humans was, confusingly, called type IIB
      3. Type IIb, which is anaerobic, glycolytic, “white” muscle that is even less dense in mitochondria and myoglobin. In small animals like rodents or rabbits this is the major fast muscle type, explaining the pale color of their meat.

      For most skeletal muscles, contraction occurs as a result of conscious effort originating in the brain. The brain sends signals, in the form of action potentials, through the nervous system to the motor neuron that innervates the muscle fiber. However, some muscles (such as the heart) do not contract as a result of conscious effort. These are said to be autonomic. Also, it is not always necessary for the signals to originate from the brain. Reflexes are fast, unconscious muscular reactions that occur due to unexpected physical stimuli. The action potentials for reflexes originate in the spinal cord instead of the brain.

      There are three general types of muscle contractions, matching the types of muscles: skeletal muscle contractions, heart muscle contractions, and smooth muscle contractions.

      Skeletal Muscle

      The main bulk of muscular tissue of our body is of skeletal type. In males, the skeletal muscles organize about 40% of the body weight. There are about 656 numbers of voluntary muscles in the human body. The skeletal muscles are attached to bones by means of tendons which are found at the ends of the muscles. A tendon is a cord-like white fibrous connective tissue but it is non-elastic in nature. Some tendons are expanded and flat, forming membranous sheet-like structures known as aponeuroses.
      Each anatomical muscle is composed of a large number of elongated cells which remain parallel to the long axis of the muscle and grouped in several bundles which are called fasciculi. The whole muscle, the individual fasciculi and the individual muscle fibers remain participated by connective tissue coverings. They are known as epimysium, perimysium and endomysium respectively. These coverings are interconnected. They are forming a continuous framework which serves to bind the individual fibers together and to integrate their action.

      Structure of skeletal muscle :

      Skeletal muscle is made up of numerous muscle fibers. Every muscle fiber is a single elongated cell. They are cylindrical in shape. The fibers are un-branched, having no syncytial bridges in between them. The cell membrane of a muscle fiber is named sarcolemma. Under ordinary microscope, the skeletal muscle fibers appear to be diagonally striated due to the presence of alternate dark and light diagonal bands along their length. For this reason, the skeletal muscles are also called striated muscles. Each skeletal muscle fiber is multinucleated. The nuclei are flattened and oval or elongated in shape and they lie peripherally in the cell i-e., just beneath the sarcolemma of the muscle fiber. The cytoplasm of the muscle fiber is divisible into three parts. Those are : -
      [1J Sarcoplasm,
      [2] Myofibrij
      [3] Sarcotubular system.

      Sarcoplasm :

      Sarcoplasm is the fluid part of cytoplasm of muscle cells similar to the cytoplasm of other cells,containing several mitochondria, small Golgi bodies, endoplasmic reticulum etc.The smooth endoplasmic reticulum of muscle cells is highly developed and is called sarcoplasmic reticulum. Unlike the cytoplasm of other cells, the sarcoplasm of muscle cells stores glycogen which is a polysaccharide and myoglobin which is a hemoglobin-like pigment.

      Myofibril :

      In a sarcomere, the region between myosin filament terminals and Z-line of each side is the half I-band where only actin filaments are present. The region covering throughout the length of myosin filaments is the A-band (where actin filaments are also present surrounding the myosin) and the central part of the myosin filaments (which is not covered by actin filaments) establishes the H-band.
      In the myofibrils, in addition to the two chief muscle proteins, actin and myosin, two other proteins called tropomyosin and troponin are also found that remain attached to the actin filaments.

      Sarcotubular system :

      The sarcoplasm of muscle cells possess a specially developed system of tubules known as sarcotubular system. It is also designated as the conducting system of the skeletal muscle cells because it helps in transmission of impulse all over the muscle cells. The sarcotubular system consists of two kinds of tubules— transverse tubules and longitudinal tubules.
      Transverse tubules-The sarcolemma of muscle fibres invaginates transversely at intervals to form some tubular structures these are called transverse tubules. In mammalian skeletal muscle fibers the transverse tubules pass through the junction of A and I bands, on the other hand in amphibian skeletal muscles Transverse-tubules pass through the Z-lines.

      Longitudinal tubules-

      The smooth endoplasmic reticulum of muscle cells are specially developed and modified into some tubules that remain arranged longitudinally between the adjacent transverse tubules. These are called longitudinal tubules or in short L-tubules. The L-tubules arborize to form a reticulum (or network) at the center of the sarcomere, hence they are collectively called sarcoplasmic reticulum. The peripheral ends of the L-tubules expand to form terminal cisternae that remain in contact with the transverse-tubules.

      Skeletal System Function


      The first and most apparent function of the skeletal system is to provide a framework for the body. The presence of a firm bony skeleton allows the organism to have a distinctive shape adapted towards a particular lifestyle. For instance, in a fast-moving animal like the cheetah, the skeleton contains long, thin limb bones and an extremely flexible spine. The structure of the skeleton also allows it to absorb the impact of running at high speeds.

      The bones of birds are hollow, light and create a streamlined body adapted for flight. Many animals even have sexual dimorphism in their skeletons. In humans, while this dimorphism is fairly limited, there are differences in the angle of the pelvic bones, to accommodate pregnancy.

      Integration with the Muscular System


      The next obvious function of the skeletal system is the role it plays protecting the fragile internal organs. In humans, this is seen in the skull, which surrounds the brain completely. It is also exhibited by the ribcage, which surrounds the lungs and heart but still allows for expansion. Even invertebrates like snails and prawns often have hard exoskeletons to protect themselves from predators.

      The rigid endoskeleton allows the body to rise up above the ground or stand upright, and bears the weight of the organism, and provides the scaffolding for movement. Muscles generate the force required to move bones at joints. Muscle fibers contain actin and myosin, two protein filaments that can slide past each other to change the length of the muscle. When a nerve impulse arrives at the neuromuscular junction, it signals the muscle to contract. The force generated by the contracting muscle either pulls two bones together or apart, based on the nature of the interaction between the muscle and joint.

      Blood Cell Production

      The central part of a bone contains the bone marrow, the primary site for blood cell production in adult humans. There are two types of bone marrow in adults. Around 50% is red bone marrow containing hematopoietic stem cells and supportive tissue. The rest is yellow bone marrow made of fat and its proportion increases with age.

      Bone marrow will revert to a higher proportion of red marrow if the body suffers an injury and needs to create more red blood cells. The bone marrow composition also changes during pregnancy and lactation in mammals. Over the course of gestation, blood volume increases by about 1.5 liters, and even the concentration of red blood cells and white blood cells increase.

      Production of other Cell Types

      In addition to producing red blood cells, bone marrow within the skeletal system is the production site of a number of other cells. These include lymphocytes, which are immune cells that travel the lymphatic system. In addition to providing immune functions, the skeletal system is also responsible for hosting stem cells which can differentiate into muscle cells, cartilage-producing cells, and cells that create bone (osteoblasts).

      Osteoblasts in bone also have an endocrine function, secreting a hormone called osteocalcin. It requires vitamin K to be synthesized and is an anabolic hormone. It mediates an increase in insulin levels and increases the sensitivity of the body to insulin. Osteocalcin contributes to an increase in bone mass and bone mineralization.

      Storing Minerals

      The bones of the skeletal system act as a storehouse for calcium ions, changing the quantum of mineralized deposits within bones to maintain plasma calcium ion concentration within a narrow range. Calcium ions can affect crucial sodium ion channels in the plasma membrane of every cell, thereby affecting overall homeostasis.

      For this reason, changes to the concentration of calcium ions have particularly adverse effects on excitable cells in the nervous system, and in cardiac, skeletal and smooth muscle. Different interacting hormones maintain the balance of calcium ions in the plasma and bones, especially the parathyroid hormone secreted from the parathyroid glands in the neck.


      M. Navarro , . A. Carretero , in Morphological Mouse Phenotyping , 2017

      The Skeletal Muscle Fiber

      Skeletal muscle cells or fibers are highly elongated cells with a very elastic and resistant plasma membrane, called the sarcolemma. Fibers are characterized by the presence of numerous nuclei located at the periphery of the cell, hence muscle fibers are described as a syncytium. These cells present a large number of myofibrils ( Figs. 4-2 and 4-3 ). Myofibrils are divided into contractile units, or sarcomeres, that are delimited by Z lines, giving the typical striated appearance of the muscle fiber. Within the sarcomeres there are thick myosin and thin actin myofilaments, which are responsible for muscle contraction ( Fig. 4-3 ). Thin myofilaments consist mainly of F-actin ( Fig. 4-2 ) and other associated proteins (troponin, tropomyosin) and are anchored in the Z line, which is rich in α-actin. Other proteins are also found in the Z line, such as desmin ( Fig. 4-2 ), which helps maintain the structural and mechanical integrity of the cell, connecting the sarcomere to the sarcolemma and other subcellular structures. Each thick myofilament is formed by several myosin molecules ( Figs. 4-2 and 4-3 ), each of which consists of two heavy chains in turn associated with two light chains. The myosin filaments are anchored in the center of the sarcomere at the M line. The central zone of the sarcomere (the A band), where the myosin is situated, is darker (electron-dense) in transmission electron microscopy. By contrast, the area which contains only actin (the I band), presents a more clear or electron-lucent appearance ( Fig. 4-3 ). The H band is the area at the center of the A band where there is only myosin ( Fig. 4-2 ). In the rest of the A band the actin and myosin filaments are intertwined ( Fig. 4-3 ). In this zone, the movement of the myosin heads slides actin filaments towards the center of the sarcomere, thereby shortening the sarcomere and the muscle fiber to generate force.

      Depending on their rate of contraction, biochemistry and ultrastructure, two basic types of skeletal muscle fiber can be delineated: slow twitch fibers (type I) and fast twitch fibers (type II). Moreover, type II fibers can be subdivided into subtypes such as IIA, IIB and intermediates, depending on their content in myosin heavy chain isoforms. Type I fibers use oxidative phosphorylation as a source of energy and therefore have more mitochondria ( Figs. 4-4 and 4-5 ). Muscles with type I fibers contract more slowly and are more resistant to fatigue. Slow-twitch fibers are also more vascularized and store more lipids and myogloblin in the sarcoplasm. This, coupled with the relatively reduced density of myofibrils, gives a more reddish color to the muscle. By contrast, Type II fibers use in general, anaerobic metabolism to generate ATP. Ultrastructurally, type II fibers contain more glycogen granules and have less mitochondria and lipid droplets than type I fibers ( Figs. 4-4 and 4-5 ). Therefore, muscles that contain mainly type II fibers have a whitish color. In fact, muscles are composed of a mixture of fiber types, being a mosaic of both type I and type II fibers. The percentage of type I and II fibers in the same muscle may vary over time, changing from slow to fast, or vice versa, depending on the degree of exercise.

      Anti-myosin slow or anti-myosin fast chain antibodies can be used to differentiate type I and type II fibers, respectively ( Fig. 4-4 ). In addition, type I and II fibers can be distinguished by preincubation at acidic pH which inhibits the activity of myosin ATPase in the type II fibers ( Fig. 4-4 ). Succinate dehydrogenase (SDH) and the reduced form of nicotinamide adenine dinucleotide (NADH) can also be used to identify the oxidative potential of muscle fibers, which is higher in type I fibers ( Fig. 4-5 ). These histochemical techniques mark mitochondria in the sarcoplasm of muscle fibers ( Fig. 4-5 ). Mitochondria inside muscle fibers can also be visualized directly by transmission electron microscopy and by the use of fluorescent probes that accumulate in functional mitochondria (for example MitoTracker®) ( Fig. 4-5 ). The glycolytic activity of muscle fibers is easily identified by visualizing the activity of glycerol-phosphate dehydrogenase (GPDH). Type II fibers not only have more GPDH activity, but also a greater accumulation of glycogen which can be visualized by PAS staining ( Fig. 4-6 ).

      Muscle fibers are formed by the fusion of myoblasts, some of which remain in the mature muscle as undifferentiated cells known as satellite cells ( Fig. 4-7 ). These cells are responsible for muscle repair and muscle development after birth. Satellite cells are located beneath the basal lamina, but overlying the muscle fibers, and are thus in direct contact with the sarcolemma of muscle fibers. Satellite cells have very little cytoplasm and a nucleus distinguished by the presence of abundant heterochromatin ( Fig. 4-7 ). They express specific markers, such as the transcription factor Pax7, which are not expressed in the nuclei of mature muscle fibers ( Fig. 4-7 ).

      To produce muscle fiber contraction, calcium needs to be released into the sarcoplasm. Calcium is stored in the terminal cisternae of the sarcoplasmic reticulum bound to the acidic protein calsequestrin ( Fig. 4-8 ). Sarcoplasmic reticulum cisternae are in contact with invaginations of the sarcolemma called T tubules, where they form structures known as triads. These are located between the A and I bands of muscle fibers ( Fig. 4-8 ). T tubules can be easily identified in transmission electron microscopy, or by using an anti-GLUT4 antibody, the most important glucose transporter in the muscle fiber ( Fig. 4-8 ). Skeletal muscle plays a crucial role in maintaining blood glucose. Muscle uses glucose for energy during contractile activity and represents the most important tissue for glucose uptake and metabolism during the postprandial period. At rest, GLUT4 is stored in tubulo-vesicular structures located around the nucleus, mainly in the Golgi complex. When stimulated by muscle contractions and/or insulin, GLUT4 is translocated to the plasma membrane and T tubules ( Fig. 4-8 ).

      Skeletal muscles are supplied by arteries and veins that enter and leave the muscle belly at the level of one or more hilum (plural: hila). Muscular arteries eventually form a capillary plexus, which surrounds each of the muscle fibers, although the distribution of the capillary plexus is not equal for each fiber forming the muscle, as capillary density depends on the muscle fiber type ( Fig. 4-9 ). Type I fibers are aerobic and are more vascularized than type II fibers, which are anaerobic. For visualization, the capillary endothelial cells of mouse muscle may be labeled with an anti-PECAM-1 (CD31) antibody.

      Skeletal muscle is innervated by motor neurons which originate in the brain (cranial nerves) and the spinal cord (spinal nerves). Each muscle fiber is innervated by at least one motor neuron axon. The site of contact between the muscle fiber and the axon is a specialized synaptic junction called the motor end-plate, which is responsible for the release of the neurotransmitter acetylcholine ( Fig. 4-9 ). Each motor axon branches before reaching the end-plate contact with each muscle fiber, thereby forming several coordinated axon terminals on adjacent muscle fibers ( Fig. 4-9 ). This set of muscle fibers that are innervated by a single axon is called a motor unit. Muscle fibers act according to the law of «all or nothing», that is they are contracted or relaxed, with no intermediate states between contraction or relaxation. Therefore, the degree of contraction of a muscle depends on the number of muscle fibers that are simultaneously contracted, that is, the number of motor units that are activated.

      Watch the video: ΜΥΟΣΚΕΛΕΤΙΚΟ ΣΥΣΤΗΜΑ (July 2022).


  1. Khenan

    Let will be your way. Do, as want.

  2. Daire

    Well done, the idea is excellent and timely

  3. Voodookinos

    This idea has expired

  4. Northrop

    We are sorry that they interfere… But they are very close to the theme. Ready to help.

Write a message