From nerve signal to cross-bridge

Each power stroke of a myosin head moves the thin filament about 10 nanometres, and every cycle uses ATP.

The signal arrives

Deciding to move starts in the brain, but the order that reaches a skeletal muscle fibre comes from a motor neuron. Most of these neurons have their cell bodies in the spinal cord, and their axons can run up to about 90 cm to reach the muscle. The meeting point between the axon terminal and the fibre is the neuromuscular junction. There the terminal releases a chemical messenger, acetylcholine (ACh). It crosses a tiny gap, the synaptic cleft, and binds to receptors on the fibre membrane at the motor end-plate. The receptors are channels: when ACh binds, they open and positively charged ions flow in, making the inside of the fibre less negative.

That change opens voltage-gated sodium channels, sodium rushes in, and an action potential sweeps along the whole membrane. Meanwhile an enzyme, acetylcholinesterase, breaks down the ACh left in the cleft so that it cannot keep re-triggering the fibre.

From the membrane to calcium

A muscle fibre can be 100 micrometres thick, too wide for a signal on the surface to reach the middle quickly. So the membrane dips into the cell in narrow tubes called T-tubules (T for transverse), which carry the action potential deep inside. Each T-tubule runs between two enlarged sacs of the sarcoplasmic reticulum, the calcium store; the three together form a triad. When the action potential passes, channels in the sarcoplasmic reticulum open and calcium ions (Ca2+) flood into the sarcoplasm. This link between an electrical signal and a mechanical pull is called excitation-contraction coupling.

Five steps of the cross-bridge cycle

At rest, a strand of tropomyosin lies along the actin and covers the sites where myosin could bind, and troponin holds it there. Step 1: Ca2+ binds to troponin, which shifts tropomyosin off the binding sites. Step 2: a myosin head, already cocked and still holding ADP and phosphate from the previous cycle, binds to actin. This link is a cross-bridge. Step 3, the power stroke: the phosphate is released, the head grips more tightly and pivots toward the M line, pulling the thin filament about 10 nanometres. Then the ADP comes off, but the head is still attached. Step 4: a fresh ATP molecule binds to the head and makes it let go of actin. Step 5: the head splits the ATP into ADP and phosphate and uses the energy to swing back to the cocked position, ready to bind again further along.

Pick each step from the Step list in the model and watch the orange head. Then press Play. Many heads cycle at different moments, so some are always holding on while others reach forward, a little like a team pulling in a rope hand over hand.

Why ATP matters twice

ATP is needed at two points in the cycle. It is what makes the head let go of actin, and the energy from splitting it re-cocks the head. ATP also drives the pumps that move calcium back into the sarcoplasmic reticulum. Without ATP, myosin heads stay locked onto actin. That is the cause of rigor mortis, the stiffness of the muscles soon after death: no new ATP can be made, so the cross-bridges never release. Turn ATP off in the model and every head that can reach actin stays attached.

Switching off

Contraction stops when the motor neuron stops releasing ACh. The membrane returns to rest, the calcium channels close, and pumps move Ca2+ back into the sarcoplasmic reticulum. Troponin lets go of its calcium, tropomyosin slides back over the binding sites, and with no new cross-bridges forming, the fibre relaxes. Smooth muscle also uses calcium, but in a different way. It has no troponin, so calcium binds a protein called calmodulin, which switches on an enzyme that activates the myosin heads.

One signal, one twitch

A single action potential produces a single brief contraction called a twitch, which lasts from a few milliseconds to about 100 milliseconds depending on the muscle. Signals that arrive before the fibre has relaxed add together into a stronger pull, and at high enough rates the twitches merge into one smooth, sustained contraction called tetanus. The nervous system also grades force by how many motor units it uses. A motor unit is one motor neuron and all the fibres it supplies. In the muscles that move the eye, one neuron supplies only about six fibres, which allows very fine control. In large thigh and back muscles, one neuron can supply thousands.

This is educational material about how the body is built and works. It is not medical advice and is not for diagnosing or treating anyone.