An animal performs most of its behavior through the contraction and relaxation of muscles. Skeletal muscles have an organization in which bundles of protein filaments make up muscle cells, and bundles of muscle cells make up muscles. Muscle cells are the products of the fusion of many different cells, so each muscle cell contains many nuclei. The subcellular organization of a muscle cell also includes the previously mentioned bundles of protein filaments, called myofibrils. Lying end-to-end within these myofibrils are the actual contractile units, the sarcomeres. When the sarcomeres within a muscle cell contract, the muscle itself contracts and shortens. In the accompanying animation, we examine the mechanism by which a sarcomere shortens during contraction.
A muscle's contractile units lie within individual muscle cells, which are also called muscle fibers. Each muscle fiber contains numerous bundles of protein filaments. These bundles, called myofibrils, are organized into repeating contractile units called sarcomeres.
A sarcomere contains two types of protein filaments: actin filaments and myosin filaments. Each actin filament is attached to a Z line, which is found at either end of a sarcomere. The thick myosin filaments lie between the Z lines, but are not attached to them directly. Instead, they are held in position by a protein called titin.
The sliding filament model of muscle contraction describes the contraction and relaxation of a sarcomere. During a contraction, sarcomeres shorten. However, the actin and myosin filaments remain the same size—they simply slide past each other, changing their relative positions as the muscle contracts and relaxes.
Contraction is triggered when an action potential in a motor neuron reaches the neuromuscular junction—the junction between the neuron and the skeletal muscle. Depolarization of the axon terminal causes the release of the neurotransmitter acetylcholine into the synaptic cleft between the neuron and muscle.
The neurotransmitters trigger the muscle fiber to fire an action potential of its own. This electrical signal propagates along the muscle fiber's cell membrane. It also propagates into the cell membrane's tubular invaginations, called T tubules.
The T tubules lie adjacent to the sarcoplasmic reticulum, an organelle that consists of a membranous network of compartments. The sarcoplasmic reticulum stores calcium ions, sequestering them from the rest of the cytoplasm. When the action potential passes through the T tubules, the sarcoplasmic reticulum releases calcium into the cytosol.
The calcium ions interact with the proteins of the sarcomeres. Within the sarcomeres, the actin filaments look like two strings of pearls twisted around each other. The myosin filaments are thicker and have knoblike heads at their ends.
Actin filaments are decorated with two types of proteins. One protein, troponin, lies at regular intervals along the actin filaments. Another protein, called tropomyosin, runs the length of each actin strand. The myosin heads at this point are bound to molecules of ADP and inorganic phosphate (Pi).
After the sarcoplasmic reticulum has released calcium, the calcium ions bind to molecules of troponin. Upon binding, troponin shifts position and pulls the tropomyosin molecule aside. When tropomyosin moves, it exposes a myosin-binding site on each of the actin subunits of the actin filament.
A myosin head can now bind to the actin filament. When a myosin head binds to actin, it forms what is called a cross-bridge. Inorganic phosphate is released, triggering the myosin head, which is tightly bound to actin, to change conformation. This movement is called the power stroke, and it forces the actin and myosin filaments to slide past each other, resulting in a muscle contraction. ADP is released at the end of the power stroke.
Before the myosin head can release actin and perform additional power strokes, it must first bind to ATP. ATP is quickly hydrolyzed into ADP and Pi, returning the myosin head to the cocked position, preparing it for another cycle.
Soon after the action potential ceases, the sarcoplasmic reticulum pumps the calcium that it had released back into its interior. After calcium leaves the troponin molecules, the tropomyosin molecules again hide the myosin-binding sites. Actin and myosin filaments then slide back to their original positions, relaxing and lengthening the sarcomere. The sarcomeres of a muscle fiber contract and relax again with each signal from a motor neuron.
A muscle contraction can be explained by the cycle of molecular events that take place between actin and myosin filaments. In a single cycle, a myosin head binds to an actin filament, performs a power stroke, and then releases. Note that for the two filaments to disconnect, the myosin head must bind to a fresh molecule of ATP. After myosin releases actin, it hydrolyzes its ATP and initiates another cycle of actin/myosin interactions.
Although we focused on a single myosin head, in fact a myosin filament has many myosin heads. Each myosin filament is also surrounded by six actin filaments to which the different myosin heads can bind. Therefore, when a myosin head breaks its contact with actin, other myosin heads still connect to actin filaments and thus prevent the sarcomere from sliding back to its relaxed position.
The relaxation of the sarcomere occurs after calcium returns to the sarcoplasmic reticulum. Whereas the release of calcium from the sarcoplasmic reticulum is by a passive event in which calcium moves through ion channels, the return of calcium is an active event that requires energy. The control of muscle contraction happens at the level of free calcium in the cytoplasm—all other components involved in muscle contraction are always present and essentially await calcium ions to begin the action.