Levels of structural organisation in a typical vertebrate skeletal muscle. The muscle comprises long, cylindrical muscle fibres (about 30–100 μm across), each of which is a single multinucleate muscle cell. Each muscle contains a bundle of parallel cylindrical myofibrils (about 2–3 μm in diameter), composed mainly of the contractile material. This material is organised into repeating units, the sarcomeres, which are commonly about 2–3 μm 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 .

(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 .

Schematic diagram showing the arrangement of the SR around myofibrils in a vertebrate skeletal muscle. The (ts) forming the transverse (T) system are illustrated. The SR comprises the (tc), the (lv) and the (fc). The SR is connected to the T tubules through ‘feet’ formed by the ryanodine receptor. From Peachey .

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 .

(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 .

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. .

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 . 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 .

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 (α, β, γ and δ) with different fibre properties (α generally small and slow, δ generally large and fast). S, skin. From Chayen et al. .

(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 .

(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 .

(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.

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 (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 .

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 .

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 P_i, but these products are not released from myosin. In this M·ADP·P_i state, the heads can reattach to actin (step 3). When attached, the products ADP and P_i 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.

Stereo view of the structure of the myosin head as determined by Rayment et al. 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 α‐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.

(a) Ribbon diagram of the actin monomer structure as determined by Kabsch et al. 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. . (c) Ribbon diagram of the two‐chain coiled‐coil α‐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 .

(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 . (b) View down the muscle long axis of the A‐band unit cell in fish muscle (cf. Figure c). 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. . Copyright © 1997, by permission of the publisher Academic Press.

(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 and Figure a) to the observed density in (a), which is shown here as a mesh of ‘chicken wire’. From Harford et al. .