Structural organization of the muscle
Skeletal muscle has a hierarchical structure. A whole muscle consists of muscle fibers (myocytes), each fiber contains myofibrils, and myofibrils are built from thin and thick myofilaments.
- Thick filaments are formed by myosin molecules. A myosin molecule consists of a tail and a head; the head possesses ATPase activity and is capable of hydrolyzing ATP to ADP.
- Thin filaments are composed of actin and the regulatory proteins troponin and tropomyosin.
Tropomyosin spirals around the actin filament and, at rest, blocks the active sites of actin, preventing its interaction with myosin. Troponin is a globular protein consisting of three subunits:
- Subunit T — binds troponin to tropomyosin;
- Subunit C — binds Ca²⁺ ions;
- Subunit I (inhibitory) — binds troponin to actin.
Sarcomere as the functional unit
The structural and functional unit of a myofibril is the sarcomere — the segment between two Z-discs (transverse protein plates). It is at the level of the sarcomere that the interaction between actin and myosin occurs, which underlies contraction.
Terminologically, many structures within a muscle cell share the root "sarco-": the cytoplasm is called the sarcoplasm, the plasma membrane is the sarcolemma, and the endoplasmic reticulum is the sarcoplasmic reticulum.
Excitation-contraction coupling
Contraction is triggered by a nerve impulse arriving via a motor neuron axon to the muscle fiber. At the neuromuscular junction, excitation is transmitted to the postsynaptic membrane, after which an action potential propagates along the sarcolemma.
The sarcolemma forms invaginations into the interior of the fiber known as the T-tubule system. Through these, the action potential reaches specialized membrane dihydropyridine receptors (DHPRs). DHPRs are mechanically coupled to ryanodine calcium channels of the sarcoplasmic reticulum.
Conformational changes in DHPRs upon T-tubule depolarization lead to the opening of calcium channels, and Ca²⁺ flows from the sarcoplasmic reticulum into the sarcoplasm.
Molecular mechanism of contraction
Free Ca²⁺ binds to troponin subunit C. This induces conformational changes in the troponin-tropomyosin complex and its displacement, thereby exposing the active sites on actin.
- The myosin head attaches to the exposed actin site, forming a cross-bridge.
- ATP is hydrolyzed into ADP and inorganic phosphate; the released energy is utilized for the power stroke of the myosin head.
- Actin and myosin filaments slide past each other, the sarcomere shortens, and the muscle contracts.
This description corresponds to the sliding filament theory: the length of the filaments does not change, only the degree of their overlap changes.
Muscle relaxation
Relaxation requires the removal of Ca²⁺ from the sarcoplasm; otherwise, contraction will persist. The following processes take place:
- Dissociation of Ca²⁺ from troponin subunit C;
- Active reuptake of Ca²⁺ into the sarcoplasmic reticulum mediated by calcium ATPase (SERCA);
- Return of the troponin-tropomyosin complex to its original position and shielding of the active sites on actin;
- Detachment of myosin heads from actin — the muscle fiber relaxes.
Thus, calcium ions act as the key regulator of the contraction-relaxation cycle, while energy-dependent processes are fueled by ATP hydrolysis both during myosin head movement and calcium pump operation.
Key points
- Muscle → fiber → myofibril → myofilaments; the functional unit is the sarcomere between Z-discs.
- Thick filaments — myosin (ATPase activity of the head), thin filaments — actin with regulatory proteins troponin and tropomyosin.
- Troponin subunits: T — to tropomyosin, C — to calcium, I — to actin.
- Action potential along T-tubules activates the dihydropyridine receptor, which opens the sarcoplasmic reticulum Ca²⁺ channel.
- Binding of Ca²⁺ to troponin C displaces tropomyosin and exposes myosin-binding sites on actin.
- Contraction is executed via the sliding filament mechanism powered by ATP hydrolysis energy.
- Relaxation is accomplished by the active pumping of Ca²⁺ back into the sarcoplasmic reticulum by calcium ATPase.
- Without calcium removal, the muscle cannot relax, highlighting the central role of Ca²⁺ in regulating contraction.