Muscle contraction

Structure of skeletal muscle

• Each muscle fibre is a long, multinucleated cell with peripheral nuclei, packed with myofibrils made of repeating sarcomeres (Z line to Z line, about 2–2.5 µm at rest).

• Sliding filament theory: filaments do not shorten; they slide past each other, so the A band stays the same while I band and H zone narrow.
• Thin filament: actin with tropomyosin lying in its groove and the troponin complex (troponin C binds Ca²⁺, troponin I inhibits, troponin T binds tropomyosin). Titin anchors myosin to the Z line and gives passive elasticity; dystrophin links the cytoskeleton to the membrane (absent in Duchenne dystrophy).
• Sarcoplasmic reticulum (SR) stores Ca²⁺ bound to calsequestrin, a low-affinity, high-capacity binding protein in its terminal cisternae. A triad is one T tubule flanked by two terminal cisternae, located at the A–I junction in mammals.

Excitation–contraction coupling

• The end-plate potential triggers a muscle action potential that spreads along the sarcolemma and down the T tubules.
• Dihydropyridine receptors (L-type Ca²⁺ channels acting as voltage sensors) in the T tubule are mechanically linked to ryanodine receptors (RyR1) on the SR. Skeletal muscle needs no extracellular Ca²⁺ for this step.
• RyR1 opens; Ca²⁺ floods the cytosol and binds troponin C.
• Troponin shifts tropomyosin, uncovering myosin-binding sites on actin.
• Cross-bridge cycle: a cocked myosin head carrying ADP and Pi binds actin; release of Pi powers the power stroke; ADP leaves; ATP binds and detaches myosin from actin; ATP hydrolysis re-cocks the head.
• Relaxation: SERCA pumps Ca²⁺ back into the SR (ATP-dependent), Ca²⁺ leaves troponin and tropomyosin covers actin again. A single twitch ends when cytosolic Ca²⁺ is removed by the SR.
• Rigor mortis (begins 2–6 hours after death, maximal about 12 hours, passes off as proteins degrade over 1–3 days): without ATP, myosin cannot detach, so cross-bridges lock.
• Malignant hyperthermia: autosomal dominant RYR1 mutation; volatile anaesthetics and suxamethonium cause uncontrolled Ca²⁺ release; treat with dantrolene, which blocks RyR1.

Force, summation and energy

• Tension is greatest at the resting length, where actin and myosin overlap optimally (length–tension relationship).
• Force is increased by recruiting more motor units (size principle: small, slow units first) and by raising firing frequency: twitches summate, and at high frequency fuse into tetanus, because the action potential (2 ms) is much shorter than the twitch.
• Isometric contraction: length constant. Isotonic: the muscle shortens against a constant load.
• Energy: stored ATP (seconds), then creatine phosphate (about 10 s), then anaerobic glycolysis making lactate (1–2 minutes), then oxidative phosphorylation for endurance.
• McArdle disease (muscle glycogen phosphorylase deficiency): exercise causes cramps and myoglobinuria; in the ischaemic forearm test lactate fails to rise because muscle glycogen cannot be broken down, while blood glucose is normal because liver phosphorylase is intact.

Fibre types

• Type IIa fibres are intermediate (fast oxidative). Endurance training increases oxidative capacity; resistance training causes hypertrophy (bigger fibres, more myofibrils).
• Disuse atrophy after weeks in a plaster cast is due to shrinkage of existing fibres (protein breakdown outweighing synthesis, via the ubiquitin–proteasome pathway), not loss of fibres. Denervation causes more severe atrophy with fibrillation.

Cardiac muscle

• Branched, striated cells with one or two central nuclei, joined by intercalated discs containing desmosomes and gap junctions, so the myocardium acts as a functional syncytium.
• Ca²⁺ entering through L-type channels in the plateau triggers further SR release: calcium-induced calcium release. Removing extracellular Ca²⁺ stops cardiac contraction but not skeletal contraction.
• The long refractory period prevents tetanus. Force rises with stretch (Frank–Starling) and with sympathetic stimulation (more Ca²⁺ entry and uptake).

Smooth muscle

• Spindle-shaped cells with a single central nucleus, no sarcomeres or striations; actin attaches to dense bodies; little SR.
• Contraction: Ca²⁺ enters through voltage- or ligand-gated channels or is released from the SR by IP₃. Ca²⁺ binds calmodulin, which activates myosin light chain kinase (MLCK); phosphorylated myosin binds actin.
• Relaxation: myosin light chain phosphatase dephosphorylates myosin. Rising cAMP (β2 agonists) inhibits MLCK; rising cGMP (NO, nitrates, sildenafil) activates the phosphatase and lowers Ca²⁺.
• Latch state maintains tension with very little ATP (sphincters, vessels).
• Contractors: α1 agonists, angiotensin II, ADH (V1) and acetylcholine on M3 via Gq–IP₃. Antispasmodics such as dicyclomine and hyoscine relieve biliary and gut colic by blocking muscarinic receptors.
• Single-unit (visceral) smooth muscle (gut, uterus, ureter, bladder) has gap junctions, slow-wave pacemaker activity and contracts when stretched. Multi-unit muscle (iris, ciliary muscle, vas deferens, large arteries) is individually innervated.
• In the oesophagus, skeletal muscle in the upper third gives way to smooth muscle in the lower third, with a mixed middle third.

Tetany and calcium

Low extracellular Ca²⁺ makes nerves, not the contractile machinery, more excitable, so motor nerves fire spontaneously: carpopedal spasm, Chvostek and Trousseau signs. The classic exam case is tetany on the first day after thyroidectomy from parathyroid damage, or hypocalcaemia with hyperventilation (alkalosis increases Ca²⁺ binding to albumin).

Remember ATP detaches myosin; calcium on troponin starts skeletal contraction; calcium on calmodulin starts smooth.

Exam trap The A band never changes length; only the I band and H zone shorten.

How FCPS asks about this

• A band: whole length of the thick filaments, constant during contraction.
• Protein storing Ca²⁺ in the SR: calsequestrin; actin attaches to the Z line via α-actinin.
• Rigor mortis: no ATP to detach myosin heads.
• What ends a single contraction: Ca²⁺ pumped back into the SR by SERCA.
• Type I fibres: oxidative, fatigue-resistant, rich in myoglobin.
• Smooth muscle cell: spindle-shaped with one central nucleus; contraction via calmodulin and MLCK.
• McArdle disease: lactate fails to rise on ischaemic exercise.