Abstract
Locomotion: contraction of muscle reduces the distance between its sites of origin and insertion, thereby producing movement.
What are the functions of skeletal muscle?
Locomotion: contraction of muscle reduces the distance between its sites of origin and insertion, thereby producing movement.
Maintenance of posture and joint stability: this is achieved through tonic contraction of multiple synergistic and opposing muscle groups.
Support of soft tissues: the muscles of the abdominal wall and pelvic floor support and protect their underlying viscera.
Sphincteric function in the gastrointestinal tract and urinary tracts: skeletal muscle provides voluntary control over swallowing, defecation and micturition.
Heat production: this occurs through alterations in background muscle metabolic rate and shivering (repeated muscle contraction and relaxation).
Venous return: contraction of leg muscles aids in the generation of local pressure gradients to move venous blood towards the heart.
Describe the macroscopic and microscopic anatomy of skeletal muscle
Skeletal muscles are made up of many muscle fibres (myocytes). They are served by blood vessels and nerves and are supported by a number of connective tissue layers:
Endomysium, the thin layer of connective tissue surrounding each myocyte.
Perimysium – bundles of around 100 myocytes surrounded by perimysium are called fascicles.
Epimysium, the thick layer of connective tissue that encases the entire muscle.
At each end of the muscle, the layers of connective tissue (endomysium, perimysium and epimysium) merge to form a tendon or an aponeurosis, which usually connects the muscle to bone.
Myocytes have a number of unusual anatomical features:
Size. A muscle fibre may span the entire length of the muscle and have a diameter of up to 50 μm.
Nuclei. Myocytes are multinucleate. Nuclei are located peripherally, unlike in cardiac and smooth muscle.
Striations. Skeletal and cardiac muscle, but not smooth muscle, have a striped or ‘striated’ appearance due to regularly repeating sarcomeres (see below).
Myocytes have a number of specialised cellular features in addition to the usual complement of Golgi apparatus, mitochondria and ribosomes:
The sarcoplasmic reticulum (SR) is a modified endoplasmic reticulum (ER) that acts as an intracellular store of Ca2+ and can rapidly release and sequester Ca2+.
The transverse (T)-tubules are invaginations of the muscle surface membrane, or sarcolemma, capable of relaying action potentials deep into the myocyte interior.
Myofibrils, the contractile apparatus of the cell, are arranged in parallel with one another spanning the entire length of the myocyte. Because myofibrils are anchored to the sarcolemma at either end of the myocyte, the whole myocyte shortens when they contract.
Myofilaments – within the myofibrils are bundles of myofilaments, containing the contractile proteins actin and myosin.
Glycogen stores, which release glucose to provide energy for muscle contraction.
What is a sarcomere?
A sarcomere is the functional unit of a skeletal muscle fibre. It contains interdigitating thick, myosin-containing and thin, actin-containing filaments (Figure 54.1a). These are arranged in a regular, repeating, overlapping pattern, giving an alternating sequence of dark and light bands, resulting in a striated appearance. Key features of the sarcomere are:
Z disc, located at either end of the sarcomere, bisecting the I band.
Thick and thin filaments. The thin filaments are joined at one end to the Z disc. The thick filaments are at the centre of the sarcomere, interdigitating with thin filaments.
I (isotropic) or light band, containing the portion of the thin filament that does not overlap with the thick filament.
A (anisotropic) or dark band, the entire length of the thick filament, including regions that overlap the thin filament.
H (Heller) band, the part of the A band that contains only myosin.
Each mammalian sarcomere therefore contains one A band and two half I bands (Figure 54.1b).
Describe the key structural features of the thick and thin filaments
Key features are:
Thick filament. Each thick filament contains myosin, a large protein that has two globular ‘heads’ and a long ‘tail’. The myosin heads have distinct binding sites for actin and ATP (Figure 54.2a). Each thick filament is surrounded by six thin filaments in an approximately hexagonal arrangement
Thin filament. Each thin filament is composed of three proteins: the contractile protein actin and the regulatory proteins tropomyosin and troponin (Figure 54.2b):
– Actin is a globular protein that forms chains that are twisted together in double strands. Each thin filament contains around 300–400 actin molecules with regularly spaced myosin binding sites along its length.
– Tropomyosin is a fibrous protein chain that lies in the groove between the two strands of actin. Tropomyosin obstructs access to the myosin binding site, preventing crossbridges forming between actin and myosin.
– Troponin. This protein complex is located at regularly spaced intervals along the tropomyosin protein chain. The troponin complex is made up of three subunits:
■ Troponin T binds the troponin complex to tropomyosin (hence ‘Τ’).
■ Troponin I has an uncertain role. It may inhibit myosin ATPase activity (hence ‘I’).
■ Troponin C contains the Ca2+ binding site (hence ‘C’ for Ca2+). Binding of Ca2+ to troponin C causes tropomyosin to roll deeper into the actin groove, which uncovers the myosin binding site, allowing crossbridges to form between actin and myosin.
What is meant by ‘excitation–contraction coupling’?
Excitation–contraction coupling refers to the processes linking depolarisation of the muscle cell membrane to the initiation of myocyte contraction.
In common with neurons, the sarcolemma has excitable properties:
The myocyte resting membrane potential is typically –90 mV (see Chapter 51).
The sarcolemma has the capacity to fire action potentials (see Chapter 52): synaptic activity at the motor end plate causes depolarisation of the sarcolemma, triggering an action potential that propagates along the myocyte surface membrane.
Excitation–contraction coupling occurs as follows:
The T-tubules transmit the action potential deep into the myocyte interior and close to the sarcoplasmic reticular Ca2+ store.
The dihydropyridine receptor (DHPR) senses the depolarisation of a T-tubule. The DHPR is a modified subtype of the voltage-gated L-type Ca2+ channel; depolarisation causes a conformation change, but allows little Ca2+ to pass.1
The ryanodine receptor (RyR). The DHPR is in allosteric (physical) contact with the cytoplasmic portion of another important Ca2+ channel, the RyR. The RyR also contains an intramembrane portion embedded within the SR membrane. Following a conformation change in the DHPR, these physical connections cause the RyR to open and release Ca2+ from the SR, where Ca2+ is present at high concentration, to the sarcoplasm, where the Ca2+ concentration is low.2
Release of Ca2+ from the SR increases the intracellular Ca2+ concentration by a factor of 2000.
Ca2+ binds to troponin C, causing a conformational change of the whole troponin–tropomyosin complex. The myosin binding site is uncovered, which allows actin–myosin interaction.
