Muscles and movement: the sliding-filament model

From muscle to sarcomere

Skeletal muscles move the body by pulling on bones. A muscle is attached to bone by tendons, which are tough and inelastic, so the whole of its pull is passed to the bone, and bones meet at joints held together by ligaments. A muscle can pull but cannot push, so muscles work in antagonistic pairs across a joint, acting against an incompressible skeleton: the flexor contracts to bend the joint and the extensor contracts to straighten it, as the biceps and triceps do at the elbow.

Skeletal muscle is built in nested layers, and the levels are named in order from whole muscle down to sarcomere.

A muscle is a bundle of muscle fibres. Each fibre is a single cell, but an unusual one: it is up to several centimetres long, it is multinucleate, its cell surface membrane is called the sarcolemma, its cytoplasm the sarcoplasm, and it is packed with mitochondria. Folds of the sarcolemma run deep into the fibre as transverse tubules, and a specialised endoplasmic reticulum, the sarcoplasmic reticulum, wraps around the myofibrils and stores calcium ions.

Inside each fibre lie hundreds of myofibrils, and each myofibril is a chain of sarcomeres joined end to end at Z lines. The sarcomere is the functional unit of contraction, and the mechanism below operates within it.

Two kinds of filament fill it. Thick filaments are made of myosin, whose molecules have long tails bundled together and globular heads projecting outwards. Thin filaments are made of actin, wound with a fibrous protein called tropomyosin and studded with troponin. The thin filaments are anchored to the Z lines; the thick ones sit in the middle, held together at the M line.

Describe the drawing

Two rows of sarcomeres, relaxed above and contracted below, each drawn between three Z lines. Thick filaments sit in the middle of each sarcomere and thin filaments reach in from every Z line. Brackets under each row mark the A band, which is the same width in both rows, the I band around the shared Z line and the H zone at the centre of the thick filaments, both of which are visibly narrower in the contracted row.

Sarcomere

The functional unit of a myofibril, running from one Z line to the next.

A band

The dark band, the full length of the thick filaments, including any overlap with thin filaments.

I band

The light band, containing thin filaments only, spanning a Z line.

H zone

The lighter region at the centre of the A band, containing thick filaments only.

Sarcoplasmic reticulum

The membrane system inside a muscle fibre that stores and releases calcium ions.

The banding pattern during contraction

The changing banding pattern is the evidence for the sliding filament mechanism, and each change can be derived from what each band contains.

The A band is the length of the thick filaments. During contraction the thick filaments neither shorten nor move relative to the centre of the sarcomere, so the A band does not change. A constant A band is the direct evidence that the filaments slide rather than shorten.

The I band contains only thin filaments. As the thin filaments are pulled in towards the centre, more of their length lies inside the A band, so the region containing thin filaments alone gets shorter.

The H zone contains only thick filaments, the part of the A band that the thin filaments have not yet reached. As they slide further in, that gap closes, so the H zone gets shorter too, and in a strong contraction it can disappear entirely.

The sarcomere as a whole shortens by the same amount the I band loses, which is also the amount the H zone loses, because the Z lines are dragged towards each other. A muscle shortens because millions of sarcomeres in series each shorten by a fraction of a micrometre.

How the sliding is driven

The mechanism is a cycle, and the order of its steps carries the explanation. It begins at the neuromuscular junction.

Acetylcholine released there depolarises the sarcolemma, and the depolarisation spreads along it and down the transverse tubules into the depths of the fibre. That triggers the sarcoplasmic reticulum to release calcium ions into the sarcoplasm.

Calcium binds to troponin, which changes shape and pulls the tropomyosin aside, exposing the myosin binding sites on the actin. Until this moment the binding sites were covered and no cross-bridge could form, which is why a resting muscle does not contract despite having everything else it needs.

Describe the drawing

An animation of the myosin head cycle in five stages, drawn as a thin actin filament above a thick myosin filament carrying two heads, with a dashed mark left at the thin filament's starting position. Stage one: tropomyosin lies over the binding sites and the cocked heads cannot attach. Stage two: calcium binds troponin, tropomyosin is pulled aside and the sites are exposed. Stage three: a head attaches to the thin filament and the cross-bridge is formed, with ADP and phosphate still bound. Stage four: the head bends in the power stroke, ADP and phosphate leave, and the thin filament is dragged about ten nanometres past the dashed mark while the thick filament stays where it is. Stage five: ATP binds, the head lets go and hydrolysis re-cocks it, with the thin filament left in its new position.

A myosin head, carrying ADP and phosphate from a previous round, attaches to the exposed binding site and forms a cross-bridge. The head then bends in the power stroke, releasing ADP and phosphate and pulling the thin filament about 10 nm towards the centre of the sarcomere. An ATP molecule then binds to the head, which causes it to detach from the actin. Hydrolysis of that ATP by the head's own ATPase activity returns the head to its upright position, ready to attach further along the filament.

Hundreds of heads on each thick filament do this out of step with one another, so at any instant some are attached while others are detached and the filament is never released. As long as calcium remains and ATP is available, the cycle repeats and the filaments keep sliding.

Relaxation also requires ATP. When impulses stop, calcium ions are actively pumped back into the sarcoplasmic reticulum, which costs ATP; calcium leaves troponin, tropomyosin slides back over the binding sites, and cross-bridges can no longer form. The muscle is then lengthened by its antagonistic partner or by gravity, because a muscle can pull and cannot push.

Rigor mortis makes the role of ATP unusually clear. After death, respiration stops and ATP runs out. Without ATP the myosin heads cannot detach from actin, and without ATP calcium cannot be pumped back, so the cross-bridges stay formed and the muscles are locked rigid until the proteins themselves begin to break down.

Fibre types and the supply of ATP

Skeletal muscles contain a mixture of fibre types, and the proportions differ between muscles and between individuals. Every row of the comparison below follows from one difference: the main route by which each fibre type makes ATP.

Slow twitch fibres are built around a continuous aerobic supply: many mitochondria to make ATP, dense capillaries to bring oxygen and glucose, and myoglobin to store oxygen inside the fibre. Fast twitch fibres are built for a short burst instead, relying on anaerobic glycolysis and a large glycogen store, and they tire quickly. Accumulating lactate is the traditional exam marker of that fatigue, though the fatigue itself has several causes, phosphate build-up and ion imbalances among them, rather than lactate acting as a simple acid poison.

Describe the drawing

A horizontal bar chart of four sources of ATP for a muscle working hard, on a time axis marked at two seconds, ten seconds, thirty seconds, ninety seconds and three minutes. The ATP already in the fibre lasts about two seconds, phosphocreatine regenerates ATP for about ten, anaerobic glycolysis carries on to about ninety seconds, and aerobic respiration runs on past the right-hand edge of the chart. All four bars start at zero, because every source is in use from the first second.

The ATP a muscle contains at rest supports only a second or two of hard work. Three supplies extend it. Phosphocreatine, stored in the sarcoplasm, transfers its phosphate group directly to ADP, regenerating ATP rapidly and anaerobically for only a short period, of the order of ten seconds at maximal effort. Anaerobic glycolysis, with the pyruvate reduced to lactate, can support high power output for longer but yields only two ATP per glucose and contributes to fatigue. Aerobic respiration supplies ATP more slowly and requires oxygen delivery, but yields around 30 ATP per glucose and can sustain activity for much longer, subject to oxygen delivery, substrate availability, temperature and fatigue.