Muscle Contraction

John M Squire, University of Bristol, UK

Published online: September 2011

DOI: 10.1002/9780470015902.a0001256.pub3

Muscular contraction is one of the few biological processes that can be appreciated directly in our everyday lives. In the past few decades a detailed understanding of the underlying molecular processes that produce force and movement has been obtained. Striated muscles contain well organised repeating units called sarcomeres which each include overlapping arrays of filaments of the proteins myosin and actin. Myosin filaments have projections on their surfaces known as crossbridges. These are the myosin head parts of the myosin molecules which form the myosin filament. It is the myosin heads, which are enzymes (ATPases) which interact with actin filaments to produce force and movement. Actin filaments contain additional proteins troponin and tropomyosin which are involved in switching muscle activity on and off (muscle regulation).

Key Concepts:

  • Vertebrates have two types of striated muscle namely cardiac muscle, which drives our heart and skeletal muscles which move our skeleton.
  • Vertebrate skeletal muscles contain long thin fibres (multinucleate cells) about 20–100 m in diameter and very long (mms to cms).
  • Muscle fibres are parallel arrays of long, thin myofibrils about 2–5 m in diameter and sometimes as long as the fibres.
  • Cardiac muscle cells (myocytes) are much shorter than skeletal muscle fibres and link end-to-end to provide long lengths of muscle. They also contain myofibrils.
  • The basic repeating unit in all striated muscles is the sarcomere. In vertebrates this is about 2–2.5 m long. A myofibril is a long string of sarcomeres.
  • The sarcomere comprises overlapping arrays of myosin and actin filaments.
  • Myosin filaments are made of myosin molecules which consist of a rod-shaped region with two heads on.
  • The myosin heads projecting from the myosin filament surface can hydrolyse ATP (adenosine triphosphate; they are ATPase enzymes), a process which is accelerated when heads interact with actin to produce force and movement.
  • In striated muscles the interaction of myosin heads with actin is controlled by the proteins troponin and tropomyosin on the actin filaments.
  • It is calcium ions released by the sarcoplasmic reticulum around myofibrils in response to nervous stimulus that interact with troponin, move tropomyosin and allow the actin–myosin interaction to proceed.

Keywords: myosin; actin; crossbridge cycle; sarcomere; myosin ATPase

Figure 1. Levels of structural organisation in a typical vertebrate skeletal muscle. The muscle comprises long, cylindrical muscle fibres (about 30–100 m across), each of which is a single multinucleate muscle cell. Each muscle contains a bundle of parallel cylindrical myofibrils (about 2–3 m in diameter), composed mainly of the contractile material. This material is organised into repeating units, the sarcomeres, which are commonly about 2–3 m long. This gives the myofibrils, the fibres and the whole muscle their characteristic cross-striated appearance. The positions of the A band, I band, Z band (Z disc) and H band are shown. Adapted from Bloom and Fawcett (1975).
Figure 2. (a) Schematic diagram showing the axial organisation within the vertebrate striated muscle sarcomere. The centrally placed, bipolar myosin filaments (M) carry projections, the myosin heads, which point in opposite directions in the two halves of the filaments. The length of the myosin filaments defines the A band. Partially overlapping the myosin filaments at each end of the sarcomere are the actin filaments (A). Oppositely directed actin filaments in successive sarcomeres are linked through the Z band, or Z disc (Z). In cross-section, the sarcomere has varying appearances. At the M band (d), the hexagonal array of myosin filaments (e) is linked by cross-connections (M bridges). In the overlap region of the A band (c), the actin filaments lie on hexagonal lattice positions between the myosin filaments. At the Z band (b), the actin filaments are organised into a square lattice.
Figure 3. Schematic illustrations of the structure of actin and myosin filaments. (a) Actin filaments consist of a twisting string of actin monomers (A – light blue circles), along with tropomyosin (TM – dark blue strands) and the troponin complex (TN – dark blue circles). (b) Myosin filaments are aggregates of myosin molecules (c) in which the rod parts of myosin molecules pack to form the central backbone of the myosin filaments (green), with the myosin heads (yellow) arranged almost helically on the filament surface. Adapted from Squire (1986).
Figure 4. Schematic illustration of the structure and arrangement of titin (connectin) in the muscle sarcomere. The PEVK region is rich in the amino acids for which PEVK are the amino acid sequence codes (see text). It can be seen how different parts of the titin molecule are associated with different sarcomere components. Adapted from Labeit and Kolmerer (1995).
Figure 5. Summary of a simple mechanical representation of the myosin crossbridge (head) cycle on actin involved in force generation and movement, together with the associated states of ATP hydrolysis. The AM state (actin A and myosin M only) has no nucleotide (e.g. ATP or ADP) bound and is the ‘rigor’ state of head attachment. Addition of ATP releases the heads from actin (step 1) to form M·ATP, and while detached there is a recovery stroke (step 2) when ATP hydrolyses to ADP and inorganic phosphate Pi, but these products are not released from myosin. In this M·ADP·Pi state, the heads can reattach to actin (step 3). When attached, the products ADP and Pi are released from myosin (step 4) and there is a conformational change of the heads that leads to force production and to filament sliding if the filaments are free to move.
Figure 6. Stereo view of the structure of the myosin head as determined by Rayment et al. (1993) using protein crystallography. This is a ribbon diagram showing the protein polypeptide backbone only, not the side-chains. The top half of the structure is the motor domain, which contains the ATP-binding site and the actin-binding face (top left). The lower half of the structure is commonly known as the neck or lever arm. This consists of a long -helical part of the myosin heavy chain (blue/purple) that links back to the myosin rod at the bottom end of the structure (beyond residue 843), around which are clamped two light chains, the essential light chain (yellow) and the regulatory light chain (pink/mauve). The force-generating cycle is thought to involve an ATP-driven change in angle of the lever arm at a hinge region between the motor domain and the lever arm.
Figure 7. (a) Ribbon diagram of the actin monomer structure as determined by Kabsch et al. (1990) using protein crystallography. Note the existence of discrete subdomains: 1 (red), 2 (green), 3 (blue) and 4 (yellow). (b) Ribbon diagram of the actin monomer in (a) arranged to form the actin filament by Holmes et al. (1990). (c) Ribbon diagram of the two-chain coiled-coil -helical structure of tropomyosin about 40 nm long. (d) Model of the troponin complex, drawn to the same scale as (a)–(c), including the known structure of troponin C shown as a ribbon diagram. The rest of the oval-shaped head is troponin I and part of troponin T. The remainder of troponin T forms the rod-like tail of the complex. From Squire and Morris (1998).
Figure 8. (a) Stereo view of the quasihelical arrangement of myosin heads on myosin filaments in resting vertebrate (fish) skeletal muscle. The head shape is as in Figure 6. (b) View down the muscle long axis of the A-band unit cell in fish muscle (cf. Figure 2c). The centre-to-centre distance between adjacent myosin filaments is about 47 nm. The myosin filament backbones are shown as spiralling red/green structures in the centres of the radiating myosin head arrays (yellow). Actin filaments are shown as green. The actin-binding sites on the myosin are highlighted in blue. Reprinted from Hudson et al. (1997). Copyright © 1997, by permission of the publisher Academic Press.
Figure 9. (a) Stereo view of a three-dimensional reconstruction from actin filaments decorated with myosin heads in the absence of nucleotide (i.e. rigor). The central actin filament has one myosin head attached to each actin monomer. (b) The fit of the myosin head and actin monomer shapes (see Figure 6 and Figure 7a) to the observed density in (a), which is shown here as a mesh of ‘chicken wire’. From Harford et al. (1996).
Figure 10. (a) Illustration of the innervation of several muscle fibres (which need not be adjacent to one another) by a single motor nerve to form a motor unit. (b) Schematic diagram of motor endplate showing the motor axon surrounded by a membranous envelope (the myelin sheath; my) and terminating at the neuromuscular junction (s, sarcoplasm; mn, cell nuclei). From Squire (1981).
Figure 11. Schematic diagram showing the arrangement of the SR around myofibrils in a vertebrate skeletal muscle. The transverse tubules (ts) forming the transverse (T) system are illustrated. The SR comprises the terminal cisternae (tc), the longitudinal vesicles (lv) and the fenestrated collar (fc). The SR is connected to the T tubules through ‘feet’ formed by the ryanodine receptor. From Peachey (1965).
Figure 12. Two interleaved stereo views of the actin filament in the Ca2+-free ‘off’ state (A) and in the ‘on’ state (B) with Ca2+ ions bound. The change that occurs is a movement (leftward for the front tropmyosins) of tropomyosin from being close to subdomain 1 (dark red) of actin in (A) to being much further from subdomain 1 in (B). It is to subdomain 1 that the myosin heads need to bind to complete their ATP cycle. From Squire and Morris (1998).
Figure 13. (a) Different time scales of twitch responses in (1) a mammal gastrocnemius muscle, (2) a mammal soleus muscle and a frog muscle at (3) 10 °C and (4) 0 °C. (b) Variations in tension response in a twitch muscle with different stimuli: (A) response to a single shock, (B) response to two closely spaced shocks, (C) unfused tetanus produced by repetitive stimulation at moderate frequencies and (D) tetanus induced by shocks arriving faster than the fusion frequency. From Squire (1981).
Figure 14. Alteration of tension actively generated by the contractile apparatus as a function of the sarcomere length (b) and its interpretation in terms of the changing overlap of the thick myosin and thin actin filaments (a and c). From Gordon et al. (1966).
Figure 15. Comparative mechanical properties of frog semitendinosus muscles (a) and frog sartorius muscles (b) as a function of sarcomere length. Shown in each case are the resting tension (r), the total active tension (a) and the difference, the active increment curve (d), which represents the tension actively generated by the contractile apparatus, as in Figure 14. The position marked 3.6 is close to the sarcomere length in microns at which the myosin and actin filaments are just not overlapping. From Squire (1981).
Figure 16. Transverse section of a whole fin muscle from the plaice (magnification ×30) showing the histochemical response to reaction for myofibrillar ATP at pH 9.4. The muscle can clearly be divided into four regions (, , and ) with different fibre properties ( generally small and slow, generally large and fast). S, skin. From Chayen et al. (1987).
Figure 17. (a) Schematic diagram of the arrangement of cells (fibres) in vertebrate cardiac muscle, showing the cell branching and the intercalated discs between cells. (b) Enlargement of the intercalated disc region of a cardiac muscle showing the dense granular structure on each side of the intercellular boundary. cm, cell membrane; mit, mitochondria; Z, Z band; mf, myofilament material. From Squire (1981).
Figure 18. (a) Schematic diagram of a typical vertebrate smooth muscle showing the spindle-shaped cells with the contractile material surrounding the centrally placed nuclei. The white areas represent the location of connective tissue (mainly collagen fibrils) between the cells. The contractile material is organised into contractile units as in (d), which comprise very long actin filaments (A) with polarity reversal at rudimentary Z bands (dense bodies; Z) interacting with face-polar or side-polar myosin filaments that have myosin heads pointing in opposite directions on opposite faces of the filament. Because of this organisation, the muscle can operate over very large length changes (b), depending on the relative lengths of the actin and myosin filaments (a and m, respectively). The general shape of the smooth muscle cell (c) is defined by a network of intermediate filaments (100 Å filaments) linked by dense bodies. From Squire (1981).
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 Further Reading
    book Bagshaw CR (1993) Muscle Contraction, 2nd edn. London: Chapman & Hall.
    Geeves MA and Holmes KC (1999) Structural mechanism of muscle contraction. Annual Review of Biochemistry 68: 687–728.
    Holmes KC and Geeves MA (2000) The structural basis of muscle contraction. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 355: 419–431.
    book McComas AJ (1996) Skeletal Muscle: Form and Function. Champaign, IL: Human Kinetics.
    book McMahon TA (1984) Muscles, Reflexes and Locomotion. Princeton, NJ: Princeton University Press.
    Squire JM (1997) Architecture and function in the muscle sarcomere. Current Opinion in Structural Biology 7: 247–257.
    book Squire JM and Parry DAD (eds) (2005) Muscle and Molecular Motors. Advances in Protein Chemistry, vol. 71. San Diego, CA: Elsevier.

Related Sub-Topics:

Intracellular and Extracellular Signalling | Cell Shape | Biomolecular Interactions | Cell Signalling | Proteins: Structure, Function, Metabolism | Cell Structure
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Article Title: Muscle Contraction
 
How to Cite close
Squire, John M(Sep 2011) Muscle Contraction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001256.pub3]