15 skeletal muscle and its contraction · muscles is graded and adjusted to the load. fine...
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Part 2 Muscles
Physiology at a Glance, Fourth Edition. Edited by Jeremy P.T. Ward and Roger W.A. Linden. © 2017 John Wiley & Sons, Ltd. Published 2017 by John Wiley & Sons, Ltd. Companion website: www.ataglanceseries.com/physiology
Binding of ATP tomyosin head
Dissociation of myosin head from actin
Hydrolysis of ATP and tilt of myosin head
Binding of myosinhead to actin
Power stroke of the cross-bridge. The thin �lament moves relative to the thick �lament. Followed by the release of ADP
and cycle restarts as long as Ca2+ concentration is high
Muscle in situ
Thin �lamentThick �lament
Cross-section through sarcomere at:
M-line of thick �lament
Thick and thin�lament
Z Sarcomere Z-line
Figure 15.1 A reductionist's approach to skeletal muscle morphology, from gross anatomy (top) to the molecular level (bottom)
Figure 15.2 Sliding �lament theory
Skeletal muscle and its contraction15
Chapter 15 Skeletal muscle and its contraction
c15 33 7 February 2017 7:13 PM
33Muscles make up about 50% of the adult body mass. There are three types of muscle: skeletal (muscle attached to the skeleton); cardiac (muscle in the heart; Chapter 18) (both of these are morphologically striated or striped and are com-monly called striated muscles); and smooth (muscle involved in many involuntary processes in blood vessels, airways and gut; this type is not striated, hence its name; Chapter 18). A com-parison of the properties of the three muscle types is shown in Appendix I.
Skeletal muscleThe skeletal muscles and the skeleton function together as the musculoskeletal system. Skeletal muscle is sometimes referred to as voluntary muscle because it is under conscious control. It uses about 25% of our oxygen consumption at rest and this can increase up to 20-fold during exercise.
General mechanisms of skeletal muscle contractionThe functions of muscle tissue are the development of tension and shortening of the muscle. Muscle fibres have the ability to shorten a considerable amount, which is brought about by the molecules sliding over each other. Muscle activity is transferred to the skeleton by the tendons, and the tension developed by the muscles is graded and adjusted to the load.
Fine structure of skeletal muscle (Figure 15.1)The connective tissue surrounding the whole muscle is called the epimysium. The connective tissue that extends beyond the body of the muscle eventually blends into a tendon, which is attached to bone or cartilage. Skeletal muscle is composed of numerous parallel, elongated, multinucleated (up to 100) cells, referred to as muscle fibres or myofibres, which are between 10 and 100 μm in diameter and vary in length, and are grouped together to form fasciculi. Each fasciculus is sur-rounded by the perimysium. Each myofibre is encased by con-nective tissue called the endomysium. Beneath the endomy-sium is the sarcolemma (excitable plasma membrane). This has infoldings that invaginate the fibre interior, particularly at the motor end plate of the neuromuscular junction (Chapter 16). Each myofibre is made up of myofibrils 1 μm in diameter separated by cytoplasm and arranged in a parallel fashion along the long axis of the cell. Each myofibril is further subdi-vided into thick and thin myofilaments (thick, 10–14 nm in width, 1.6 μm in length; thin, 7 nm in width, 1 μm in length). These are responsible for the cross-striations. Thin filaments consist primarily of three proteins, actin, tropomyosin and troponin, in the ratio 7:1:1, and thick filaments consist pri-marily of myosin. The cytoplasm surrounding the myofila-ments is called the sarcoplasm. Each myofibre is divided at regular intervals along its length into sarcomeres separated by Z-discs (in longitudinal sections, these are Z-lines). To the Z-lines are attached the thin filaments held in a hexago-nal array. The I-band extends from either side of the Z-line to the beginning of the thick filament (myosin). The myosin filaments make up the A-band.
The H-zone is at the centre of the sarcomere, and the M-line is a disc of delicate filaments in the middle of the H-zone that holds the myosin filaments in position so that each one is surrounded by six actin filaments.
The thin filaments consist of two intertwining strands of actin with smaller strands of tropomyosin and troponin between them. Each strand of actin is made up of ∼200 units of globular or G-actin containing binding sites for myosin. At rest, these sites are covered by tropomyosin preventing myosin binding.
The thick filaments are made up of about 100 myosin molecules; each molecule is club shaped, with a thin tail (shaft) comprising two coiled peptide chains and a head made up of two heavy peptide chains and four light peptide chains that have a regulatory function. The ATPase activity of the myosin molecule is concentrated in the head.
The thin tails of the myosin molecules form the bulk of the thick filaments, whereas the heads are ‘hinged’ and project outward to form cross-bridges between the thick filaments and their neighbouring thin filaments. Six thin filaments surround each thick filament.
Between the myofibrils are a large number of mitochondria and glycogen granules, as found in other cells, but muscle cells have regular invaginations which project from outside the cell and wrap around the sarcomeres, particularly where the thin and thick filaments overlap. These invaginations are called transverse or T-tubules and contain extracellular fluid. The specialized smooth endoplasmic reticulum, the sarcoplasmic reticulum (SR), is enlarged to form terminal cisternae close to the T-tubules. Ca2+ is transported from the cytosol into the SR by the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA).
Like fingers of the hands sliding over one another, actin and myosin molecules slide past each other. The myosin heads bind to the actin chain and tilt. There is a constant process of binding, tilting, releasing and rebinding of cross-bridges, as well as rotation of the myosin filaments as they interact with the actin filaments and bind with the alternate myofibril in the hexagonal structure. This results in the contraction of the whole muscle. The cross-bridges are formed asynchronously so that some are active, whilst others are resting.
The interaction of actin (thin filaments) and myosin (thick filaments) brings about contraction of the muscle, which is caused by the cross-bridges, a result of the interaction of troponin and Ca2+. This mechanism is called the sliding filament theory. The contraction of muscle is triggered by release of Ca2+ from the SR (Chapter 16). Ca2+ floods out of the cisternae, where it is stored by binding reversibly with a protein, calsequestrin. This raises the concentration of calcium from 0.1 μmol/L to more than 10 μmol/L, saturating the binding sites on troponin. This results in a shift of tropomyosin, thus allowing myosin cross-bridges to bind with actin and begin the contraction cycle (Figure 15.2). The heads tilt after attachment by hydrolysing the adenosine triphosphate (ATP) energy stores, releasing adenosine diphosphate (ADP) and inorganic phosphate (Pi), which leads to a greater binding of the cross-bridges. ADP and Pi escape from the head, freeing the head for another molecule of ATP. This releases the binding of the head and, if Ca2+ is still present, the cycle continues. Otherwise, the binding is inhibited. Contraction is maintained as long as Ca2+ is high. The duration of the contraction is dependent on the rate at which SERCA pumps the Ca2+ back into the SR.
Part 2 Muscles15 Skeletal muscle and its contraction