6.1 — Muscle and the Sliding Filament

Nothing in your body pulls itself shorter. A muscle contracts because two sets of protein filaments slide past each other, exactly as two hands slide past one another when you pull them together, and the muscle shortens because the overlap increases. No protein changes length at any point.

That mechanism was worked out in 1954 by two independent teams — Andrew Huxley with Rolf Niedergerke, and Hugh Huxley with Jean Hanson, unrelated despite the shared name — who published back-to-back papers in the same issue of Nature. It explains every voluntary movement you make, why a muscle is weaker when fully stretched or fully shortened, why rigor mortis happens, and what a cramp is.

The structure, from muscle down to molecule

Skeletal muscle, level by level. The whole muscle divides into bundles, each bundle into fibres, each fibre into myofibrils, and each myofibril into a chain of sarcomeres — the repeating unit where contraction actually happens. Image: Wikimedia Commons.

A whole muscle is wrapped in connective tissue that continues beyond the muscle to become its tendon. The muscle does not attach to bone directly — its connective tissue does.

Bundles (fascicles) — visible to the naked eye as the "grain" of meat.

Muscle fibres — these are the cells. Each is a single cell 10 to 100 micrometres thick and up to about 30 centimetres long, formed by many cells fusing, so it has hundreds of nuclei spaced along its length. A single cell that long could not be controlled from one nucleus.

Myofibrils — cylindrical bundles filling the fibre, about 1 to 2 micrometres across, running its full length.

Sarcomeres — the repeating unit, about 2 micrometres long, and where everything happens.

The sarcomere

One sarcomere. Thin actin filaments are anchored at the Z-line at each end and point inward; thick myosin filaments sit in the middle and overlap them. The dark and light bands seen under a microscope are simply where the two overlap and where they do not. Image: Wikimedia Commons.

Two filaments.

Thin filaments — mostly actin, arranged as a twisted double strand of bead-like subunits. Anchored at each end of the sarcomere at a structure called the Z-line, pointing inward. Wrapped around them lie two regulatory proteins: tropomyosin, a long strand lying in the groove of the actin helix, and troponin, a complex sitting at intervals along the tropomyosin.

Thick filaments — myosin, several hundred molecules bundled together with their heads projecting outward in a spiral. Each myosin head is an enzyme that splits ATP, and it is the motor.

The striped appearance of skeletal and cardiac muscle is just this arrangement seen at low magnification. Regions where only thin filaments are present look light; regions where thick filaments are present look dark. The stripes are an optical consequence of overlap, not separate structures, and understanding that makes the classic banding terminology unnecessary to memorise.

The cross-bridge cycle

Step 1 — the head binds. A myosin head carrying the products of an already-split ATP attaches to a binding site on actin.

Step 2 — the power stroke. The head releases those products and swivels through about 45 degrees, dragging the thin filament toward the centre of the sarcomere by roughly 10 nanometres. This is where the work is done.

Step 3 — detachment requires ATP. A fresh ATP molecule binds to the head, which makes it release the actin.

Step 4 — recocking. The head splits that ATP, which returns it to its upright position ready to bind again further along.

Then it repeats, at roughly five cycles per second per head, with each thick filament carrying hundreds of heads working out of step so the pull is smooth.

Two things about step 3 deserve emphasis.

ATP is needed to let go, not to pull. The power stroke itself is driven by energy already stored in the cocked head. This is exactly why rigor mortis happens. After death, ATP production stops. The heads complete their power stroke, and then there is no ATP to detach them. Every cross-bridge locks, and the body stiffens. It begins around 2 to 6 hours after death, peaks at 12 to 24 hours, and resolves after 24 to 72 hours only because the proteins themselves begin to break down. Rigor mortis is not muscle contracting after death — it is muscle unable to release. Its timing is used in forensic estimation of time of death, with the usual caveats about temperature and activity before death.

And the same logic explains why a muscle in tetanus or severe cramp is so hard. Chapter 6.7.

What switches it on and off

At rest, tropomyosin physically covers the myosin binding sites on actin. The heads cannot attach, so nothing happens no matter how much ATP is present.

Calcium is the switch. When calcium binds troponin, troponin changes shape and drags tropomyosin aside, exposing the binding sites. Cross-bridges form and the muscle contracts.

Remove the calcium and tropomyosin slides back over the sites, and the muscle relaxes.

So contraction requires calcium and ATP; relaxation requires ATP and the removal of calcium — and removing calcium also costs ATP, because it is pumped back into storage against its gradient. Relaxation is an active process, which is not intuitive and is the reason a muscle out of energy locks rather than going limp.

From nerve signal to calcium

The sequence linking an electrical event at the surface to calcium release inside is called excitation–contraction coupling, and it depends on a piece of anatomy built for the purpose.

A T-tubule — a tube of surface membrane folded deep into the muscle fibre, running alongside the calcium stores of the sarcoplasmic reticulum. It exists so that an electrical signal on the surface arrives at every myofibril at the same instant. Image: Wikimedia Commons.

The problem it solves: a muscle fibre is up to 100 micrometres thick, and an electrical signal on its surface would take far too long to reach the deep myofibrils if it had to spread inward chemically. The result would be that the outside of the fibre contracted before the inside, which would tear it.

The solution is T-tubules — narrow tubes of surface membrane folded inward, penetrating the fibre so that the surface is effectively brought right up against every myofibril.

The sarcoplasmic reticulum — a specialised smooth endoplasmic reticulum (Chapter 1.5) — wraps around every myofibril and stores calcium at concentrations roughly 10,000 times higher than the cytosol.

The sequence:

1. An action potential arrives at the muscle fibre membrane.
2. It travels down the T-tubules into the fibre's depth.
3. A voltage sensor in the T-tubule membrane physically pulls open a calcium release channel in the adjacent sarcoplasmic reticulum. The two proteins are in direct mechanical contact — this is a lever, not a chemical messenger, which is why it is so fast.
4. Calcium floods out into the cytosol.
5. Calcium binds troponin, tropomyosin moves, contraction happens.
6. Calcium pumps in the sarcoplasmic reticulum membrane return it to storage, spending ATP.
7. The muscle relaxes.

The whole sequence takes a few milliseconds.

Malignant hyperthermia is what happens when that release channel is faulty. A mutation makes it hypersensitive to certain anaesthetic gases and to the muscle relaxant suxamethonium. On exposure, calcium pours out uncontrollably, every muscle contracts, and the ATP consumed generates enormous heat — body temperature can rise by 1 °C every five minutes, past 43 °C. Rigidity, acidosis, high potassium and cardiac arrest follow.

It is inherited as autosomal dominant, so it runs in families, and the mortality was around 80 percent before treatment existed. Dantrolene, which blocks that calcium release channel, dropped it to under 5 percent, and it is stocked in every operating theatre. This is why anaesthetists always ask whether anyone in your family has had a problem with an anaesthetic — it is not a formality, and the answer can be the difference between a routine operation and a crisis.

How force is controlled

A single fibre contracts fully or not at all. Graded force comes from two mechanisms.

Recruitment — using more motor units. A motor unit is one motor neuron plus every fibre it supplies, and all of them contract together. The size of a motor unit determines how precise the control is. Eye muscles have units of 3 to 10 fibres, giving extremely fine control. The gastrocnemius has units of over 1,000 fibres, giving power with coarse control.

And recruitment follows a fixed order — small units first, then progressively larger ones. This is the size principle, and it means light tasks are done by the small precise units and large units are only brought in when needed. It happens automatically because smaller motor neurons are more easily excited, so a given input reaches their threshold first. Nothing in the brain has to decide it.

Rate coding — firing faster. A single stimulus produces a twitch. Stimuli arriving before the previous twitch has relaxed sum together, and at high enough frequency the twitches fuse into a smooth sustained contraction called tetanus, producing three to five times the force of a single twitch. All normal sustained contractions are tetanic, which is why a held contraction feels smooth.

The length–tension relationship. Force depends on how much the filaments overlap.

• Too stretched — little overlap, few cross-bridges, weak.
• Optimal length — maximum overlap without the thin filaments colliding. Strongest.
• Too shortened — thin filaments from opposite ends overlap each other and interfere. Weak.

Joints are arranged so that muscles operate near optimal length through their normal range, and this is why you are much weaker at the extremes of a movement. Try lifting something with your elbow fully straight or fully bent and the difference is obvious.

Types of contraction

Isotonic concentric — the muscle shortens and the load moves. Lifting a weight. Isotonic eccentric — the muscle lengthens while still generating force, controlling a load that is winning. Lowering a weight slowly; the quadriceps going downstairs. Isometric — force with no change in length. Holding a weight still.

Eccentric contraction deserves attention because it is where most muscle injury happens. A muscle can produce roughly 20 to 60 percent more force eccentrically than concentrically, because cross-bridges are being forcibly detached and additional passive elements resist. The high force with fewer active fibres is what damages the fibres, and eccentric work is the main cause of delayed-onset muscle soreness (Chapter 1.6).

It is also therapeutically useful. Eccentric loading programmes are the best-evidenced treatment for tendon problems such as Achilles and patellar tendinopathy — deliberately loading the tendon in the way that stresses it most, which is counter-intuitive and works.

Fibre types

Not all muscle fibres are the same, and the difference is genuinely useful to understand.

	Type I (slow)	Type IIa (fast oxidative)	Type IIx (fast glycolytic)
Speed	Slow	Fast	Very fast
Fatigue	Very resistant	Moderate	Fatigues fast
Energy source	Aerobic	Both	Anaerobic
Mitochondria	Many	Many	Few
Colour	Red (myoglobin)	Red-pink	Pale
Used for	Posture, endurance	Middle distance	Sprinting, lifting

The colour difference is myoglobin, an oxygen-storing protein related to haemoglobin. This is exactly why chicken has dark leg meat and white breast meat: chickens walk constantly and rarely fly, so the legs are slow-twitch and the breast is fast-twitch. In migratory ducks, which fly for hours, the breast is dark.

Every muscle contains a mixture, in proportions varying with the muscle's job — postural muscles are slow-dominant, and the ratios differ between individuals. Elite marathon runners have around 80 percent slow fibres in their leg muscles; elite sprinters around 70 percent fast. How much of that is trainable and how much is genetic is an old argument; training clearly shifts IIx toward IIa and changes the metabolic properties considerably, while conversion between type I and type II is limited.

Motor units are homogeneous — all fibres in one unit are the same type, because the nerve determines the type. Cross-connect a slow nerve to a fast muscle experimentally and the muscle changes type.

Smooth and cardiac muscle, briefly

Smooth muscle uses the same actin and myosin but with no sarcomeres, so it has no stripes. The regulatory mechanism is different — calcium acts through a different protein, not troponin — and it can maintain tension for long periods at very low ATP cost, which is exactly what a blood vessel or a sphincter needs. It also responds directly to stretch, hormones and local chemicals without any nerve input, which is why the gut keeps working after transplantation and why blood vessels autoregulate.

Cardiac muscle is striped like skeletal muscle but its cells are joined electrically, so the whole tissue behaves as one (Chapter 4.2). It cannot be tetanised, because its action potential lasts almost as long as its contraction, so the muscle has relaxed before another impulse can arrive. That is a safety feature: a heart that could go into sustained contraction would stop pumping (Chapter 7.3).

What the next page fixes

Contraction begins with an action potential arriving at the muscle. Chapter 6.2 covers the junction where a nerve hands its signal to a muscle — the most studied synapse in the body, the target of nerve gases, curare, botulinum toxin and every drug used to paralyse a patient for surgery, and the site of the disease that first revealed how it works.