Skeletal Muscle: Histology, Contraction, and Clinical Disorders

Overview

Skeletal muscle is a striated, voluntary muscle that makes up ~40-50% of total body mass. It is organized hierarchically from whole muscle → muscle fascicles → muscle fibers (cells) → myofibrils → sarcomeres → filaments (actin and myosin).

Hierarchical Organization

Muscle → Fascicle → Fiber

• Muscle: Whole organ (e.g., biceps brachii) wrapped in epimysium (dense connective tissue)
• Fascicle: Bundle of muscle fibers wrapped in perimysium
• Muscle fiber (cell): Long, cylindrical, multinucleated cell wrapped in endomysium

Fiber → Myofibril → Sarcomere → Filaments

• Myofibrils: Long cylindrical organelles filling the fiber; aligned in parallel; give the striated appearance
• Sarcomere: Basic contractile unit, bounded by Z discs

Sarcomere Components

• Z disc: Anchors thin filaments (actin); defines sarcomere boundaries
• I band: Region of thin filaments only (light)
• A band: Region of thick filaments (myosin); entire thick filament length
• H zone: Center of A band with thick filaments only
• M line: Center of sarcomere; links thick filaments together

Memory aid: "Zee Is A Heavy Man" (Z disc, I band, A band, H zone, M line)

Molecular Components

Thick Filaments (Myosin)

• Myosin II structure: Two heavy chains (tail + heads) + four light chains
• Myosin heads: Contain ATPase activity and actin-binding sites
• Form the A band

Thin Filaments (Actin)

• Double helix of G-actin monomers
• Tropomyosin: Blocks myosin-binding sites at rest
• Troponin complex:
  • TnC: Binds calcium (initiates contraction)
  • TnT: Binds tropomyosin
  • TnI: Inhibits contraction

Sarcoplasmic Reticulum (SR) and T-Tubules

• Sarcoplasmic reticulum: Modified smooth ER; stores Ca²⁺; terminal cisternae
• T-tubules: Invaginations of sarcolemma that carry action potentials deep into the fiber
• Triad: T-tubule + two terminal cisternae

Sliding Filament Mechanism of Contraction

1. Action potential arrives at the neuromuscular junction (acetylcholine released, end-plate potential)
2. AP travels along sarcolemma and into T-tubules
3. Dihydropyridine receptors in T-tubule activate ryanodine receptors on SR → Ca²⁺ release
4. Ca²⁺ binds TnC → conformational shift in troponin → tropomyosin moves → exposes myosin-binding sites on actin
5. Myosin head (already bound to ATP) hydrolyzes ATP → ADP + Pi bound; head "cocks"
6. Myosin binds actin → cross-bridge formation
7. Power stroke: Pi released, head pivots, slides thin filament
8. ADP released, new ATP binds → myosin detaches
9. Cycle repeats until Ca²⁺ removed

Excitation-Contraction Coupling

• Ca²⁺ pumped back into SR by SERCA (sarcoplasmic reticulum Ca²⁺ ATPase)
• Relaxation requires energy (ATP) for SERCA
• Rigor mortis: After death, ATP is depleted → myosin stays attached to actin → stiffness

Muscle Fiber Types

Type I (Slow-twitch, red)

• High myoglobin (red color)
• Many mitochondria, oxidative phosphorylation
• Slow contraction, fatigue-resistant
• Examples: Postural muscles (soleus), long-distance runners

Type II (Fast-twitch, white)

• Type IIa: Fast-oxidative-glycolytic; intermediate
• Type IIb: Fast-glycolytic; quick, fatigue easily; sprinters
• Lower myoglobin, fewer mitochondria, more glycogen

Motor Units

• One motor neuron + all muscle fibers it innervates
• Small motor units (1-3 fibers per neuron): Extraocular muscles — fine control
• Large motor units (1000+ fibers per neuron): Gastrocnemius — gross movement
• All fibers in a motor unit are the same type

Clinical Disorders

Muscular Dystrophies

• Duchenne muscular dystrophy (DMD)
  • X-linked recessive; dystrophin gene mutation (Xp21)
  • Onset age 2-5; calf pseudohypertrophy, Gowers sign
  • Death by age 20-30 from respiratory/cardiac failure
  • Elevated CK (early), absent dystrophin on biopsy
• Becker muscular dystrophy: Less severe, partial dystrophin

Myasthenia Gravis

• Autoantibodies against postsynaptic ACh receptors at NMJ
• Fatigable weakness: worsens with use, improves with rest
• Tensilon test: Edrophonium (short-acting AChE inhibitor) briefly improves strength
• Ice pack test: Ice on ptotic eyelid improves ptosis
• Associated with thymoma (50%) and other autoimmune diseases

Lambert-Eaton Myasthenic Syndrome

• Antibodies against presynaptic voltage-gated Ca²⁺ channels
• Weakness IMPROVES with repeated use (opposite of MG)
• Often paraneoplastic (small cell lung cancer)

Polymyositis and Dermatomyositis

• Polymyositis: CD8+ T-cell mediated muscle inflammation
• Dermatomyositis: CD4+ mediated with skin findings (heliotrope rash, Gottron papules)
• Elevated CK, proximal muscle weakness

Rhabdomyolysis

• Skeletal muscle breakdown → myoglobinuria → acute kidney injury
• Causes: Crush injury, prolonged immobilization, statins, cocaine, intense exercise
• Dark "tea-colored" urine, elevated CK

Key Takeaway

Skeletal muscle's striated appearance comes from the precise arrangement of actin and myosin in sarcomeres. Memorize: I band = thin only, A band = thick (and thin where overlapping), H zone = thick only, M line = center, Z disc = boundary. DMD vs MG vs LEMS is a classic exam trio.