Duchenne Muscular Dystrophy and Muscle Fibers Anatomy

Myofibrils and Sarcomeres

• Myofibrils consist of an end-to-end repetitive arrangement of sarcomeres
• The A and I banding pattern in sarcomeres is due to the regular arrangement of thick and thin myofilaments
• The dark A band is bisected by a less dense, or light, region called the H band
• The M line contains a myosin-binding protein myomesin and creatine kinase

Thick Filaments

• Thick filament consists primarily of myosin molecules
• Myosin is a large complex (~500 kDa) with two identical heavy chains and two pairs of light chains
• Thick myosin filaments are 1.6-μm long and 15-nm wide and occupy the A band at the middle region of the sarcomere

Thin Filaments

• Thin filament primarily consists of polymerized actin molecules coupled with regulatory proteins and other thin filament–associated proteins
• G-actin is a small, 42 kDa molecule that polymerizes to form a double-stranded helix, the F-actin filament

Skeletal Muscle

• Skeletal muscle consists of muscle fibers, which are long, cylindrical multinucleated cells with diameters of 10-100 μm
• Elongated nuclei are found peripherally just under the sarcolemma
• A small population of reserve progenitor cells called muscle satellite cells remains adjacent to most fibers of differentiated skeletal muscle

Organization of a Skeletal Muscle

• Thin layers of connective tissue surround and organize the contractile fibers in skeletal muscle
• The epimysium, an external sheath of dense irregular connective tissue, surrounds the entire muscle

Sarcoplasmic Reticulum and Transverse Tubule System

• The membranous smooth ER, called here sarcoplasmic reticulum, contains pumps and other proteins for Ca2+ sequestration and surrounds the myofibrils
• Calcium release from cisternae of the sarcoplasmic reticulum through voltage-gated Ca2+ channels is triggered by membrane depolarization produced by a motor nerve

Mechanism of Contraction

• Contraction occurs when thin actin filaments slide over thick myosin filaments
• Actin filaments enter the A band, the H band narrows, and the sarcomere becomes shorter
• The lengths of actin and myosin do not change, but their positions change, causing the I bands to narrow and the length of the A band to remain unchanged

Motor Innervation

• Skeletal muscle fibers are richly innervated by motor neurons that originate in the spinal cord or brainstem
• Motor nerves branch out within the perimysium, where each nerve gives rise to several unmyelinated terminal twigs that pass through endomysium and form synapses with individual muscle fibers

Sensory Innervation

• Striated muscles contain sensory receptors acting as proprioceptors providing the central nervous system (CNS) with data from the musculoskeletal system
• Proprioceptors detect increases in tension and help regulate the amount of effort required to perform movements that call for variable amounts of muscular force

Skeletal Muscle Fiber Types

• There are three types of skeletal muscle fibers: Type I (slow oxidative), Type IIa (fast oxidative glycolytic), and Type Iıb (fast glycolytic) fibers
• Type I fibers are adapted for slow contractions over long periods without fatigue, having many mitochondria, many surrounding capillaries, and much myoglobin
• Type IIa fibers are intermediate fibers seen in fresh tissue, with many mitochondria and high myoglobin content
• Type Iıb fibers are capable of anaerobic glycolysis