Sarcomere

How is a sarcomere structured?

A sarcomere is a section of a myofibril located between two adjacent Z-lines (telophragms). Thin filaments attach to these boundaries. Hundreds and thousands of such units are arranged sequentially within a single myofibril.

Main structural elements:

• Myosin — thick filaments. They have a mobile head with enzymatic activity (ATPase).
• Actin — thin filaments attached to the Z-discs. They contain binding sites for myosin.
• Tropomyosin — thin filaments of a regulatory protein on the surface of actin.
• Troponin — a regulatory protein located on actin; at rest, it blocks the interaction between actin and myosin.
• T-tubules — a system of transverse tubules for conducting excitation into the cell.

The ratio of thin to thick filaments is approximately 4 to 1. In cross-section within the overlap zone, a strict hexagonal packing is observed: 6 thin filaments are grouped around one thick filament, and 3 thick filaments around one thin filament.

Topography and zones (from edge to edge):

1. Z-line — the boundary of the sarcomere.
2. I-half-band (light) — contains only thin myofilaments.
3. Dark part of the A-band — the overlap zone, where both thick and thin filaments are present.
4. H-zone — a light stripe in the center of the A-band, containing only thick myofilaments. The M-line runs through the middle.
5. Dark part of the A-band.
6. I-half-band (light).
7. Z-line — the opposite boundary.

It is precisely this zonal distribution that creates optical heterogeneity. The alternation of light I-bands and dark A-bands creates the characteristic cross-striation visible under a light microscope in an entire muscle fiber.

Mechanism of muscle contraction

The mechanism of sarcomere function is based on the sliding filament theory. Under the action of $Ca^{2+}$ ions, filament sliding occurs.

Stages and zone dynamics:

• The myosin head performs a rowing movement.
• The actin filament is pulled toward the center of the sarcomere, sliding along the myosin filament.
• Z-discs move closer together, and the overall length of the sarcomere decreases.
• Thin filaments penetrate deeper between thick ones: the light I-bands and H-zone narrow, while the dark parts of the A-band (overlap zones) widen.
• The total width of the A-band remains unchanged because the length of the thick filaments does not change.

The maximum limit of contraction occurs when the I-bands completely disappear and the thick filaments abut the Z-lines. At initial dimensions (I-band — 0.8 µm, A-band — 1.5 µm), the muscle can shorten by approximately 35% of its length.

Dependence of contraction force on length:

• With excessive stretch, the number of cross-bridges between actin and myosin drops, which decreases the contraction force.
• With no load (shortening), actin filaments overlap each other, the number of effective bridges also drops, and the contraction force falls.

Clinical significance: hypertrophic cardiomyopathy

In HCM, pathogenic variants in sarcomeric protein genes are found. In 15–20% of cases, the cause of HCM is pathogenic variants in genes encoding cytoskeletal proteins, ion channels, Z-discs, and other intracellular structures.

Pathogenesis:

1. Calcium homeostasis is disrupted, and the sensitivity of myofilaments to $Ca^{2+}$ increases.
2. Contractility is impaired: the sarcomere contraction force during systole increases, while the degree of relaxation during diastole decreases.
3. Energy deficit develops due to the increased ATP demand of the cardiomyocyte.
4. Intracellular processes malfunction, and compensatory embryonic programs of hypertrophic growth are reactivated.
5. At the cellular level, the synthesis of embryonic forms of sarcomeric proteins increases, kinase signaling cascades are activated, fibroblasts proliferate with transformation into myofibroblasts, and an imbalance occurs in the collagenolysis system.

Genetic features: Most pathogenic variants are unique: they have been described once or in isolated patients. The frequency of each specific substitution among all causes of HCM does not exceed 1%. In 5–7% of cases, multiple mutations occur: the presence of 2, 3, or more pathogenic variants. Most often, these are combinations of mutations in sarcomeric protein genes. They are characterized by an earlier onset, often in childhood, marked hypertrophy of the interventricular septum, and a high risk of sudden cardiac death.

Class and exam questions

What else to study on this topic

• Myofibril
• Actin and myosin
• Mechanism of muscle contraction
• Hypertrophic cardiomyopathy

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.