Muscle Contraction – Sarcomere, Myofilaments & Sliding Filament Theory

Structure and Function of Myofilaments

• Two primary filament types inside each sarcomere
  • Thick myofilaments → built primarily from the protein myosin
  • Thin myofilaments → composite of actin, tropomyosin, and troponin
• Associated regulatory/energy molecules
  • \text{ATP} (depicted as a star-shape in diagrams)
  • \text{Ca^{2+}} ions (red spheres) released from the sarcoplasmic reticulum (SR)
• Understanding every component is essential for describing contraction

Sliding Filament Theory (Macro View)

• Sarcomere shortening = Z-lines move closer as thin & thick filaments slide past one another
• The process is visualized as filaments “sliding,” not contracting themselves
• Net effect → overall myofibril and thus the entire muscle fiber shortens

Thick Myofilament (Myosin) Details

• Gross appearance under EM: bar-like core with many projecting heads
• Individual myosin molecule resembles a two-headed golf club
  • Tail (shaft)
  • Neck (hinge 1) → permits bending of the tail
  • Head (hinge 2) → can pivot independently; site of force generation
• Two joints → analogous to two finger joints; enable the “reach-pull-release” cycle
• Terminology
  • Cross-bridge = temporary physical link between a myosin head (thick) and an actin site (thin)
• Functional sites on the head
  • Actin-binding site → docks into actin’s pocket (olive “pimento” analogy)
  • ATP-binding site → binds & hydrolyzes ATP; fuels conformational change

ATP: Cellular Fuel for Contraction

• Formation: \text{ADP} + P_i + \text{Food Energy} \; \rightarrow \; \text{ATP}
• Hydrolysis during work: \text{ATP} \; \rightarrow \; \text{ADP} + P_i + \text{Energy}
• Energy released places myosin head in a high-energy (cocked) conformation
  • Mousetrap analogy: loading the spring = ATP hydrolysis; trap snap = power stroke
• Post-stroke: ADP & P_i are low-energy by-products and dissociate
• If ATP biochemistry feels rusty, revisit Ch. 2–3 (cellular energetics)

Thin Myofilament Components

• Actin
  • Appears as two helical strings of bead-like subunits
  • Each bead (G-actin) has a depression = myosin-binding pocket
• Tropomyosin
  • Long, rope-like regulatory protein
  • Lies in the actin groove; covers the myosin-binding sites in resting muscle
• Troponin
  • Three-part complex (snowman analogy)
  1. TnT – binds tropomyosin
  2. TnC – binds \text{Ca^{2+}}
  3. TnI – inhibits actin–myosin interaction
  • Regulates exposure of binding sites via \text{Ca^{2+}}-dependent conformational shift

Role of Sarcoplasmic Reticulum & Calcium

• SR envelops each myofibril; specialized for \text{Ca^{2+}} storage
• Upon excitation
  • \text{Ca^{2+}} floods out of SR → diffuses to thin filament
  • Binds troponin C → pulls tropomyosin aside → exposes actin pockets
• Exposure permits myosin heads (already energized by ATP) to form cross-bridges

Sequence of Events (Micro View)

1. Resting state
   • Tropomyosin covers actin pockets; no cross-bridges
2. Excitation at neuromuscular junction triggers SR to release \text{Ca^{2+}}
3. Ca^{2+}–Troponin binding → tropomyosin shifts → pockets revealed
4. Cross-bridge formation
   • Myosin (high-energy conformation) docks to actin
5. Power stroke
   • Head pivots, pulling thin filament toward sarcomere center → Z-lines converge
6. ADP/P_i release
7. ATP binding to myosin → cross-bridge detaches
8. ATP hydrolysis resets head → cycle repeats as long as \text{Ca^{2+}} & ATP are present

Classroom / Thought Experiment

• Instructor demonstration: students line up as alternating thick & thin filaments
  • "Myosin" students (with arms as heads) grab "Actin" students & walk them inward
  • Visually conveys coordinated shortening of sarcomere stack
• Helpful group size: ≥ 5–6 participants for meaningful visualization

Practical & Clinical Relevance

• Proper ATP supply & \text{Ca^{2+}} regulation are critical → defects lead to muscle weakness or spasm (e.g., hypocalcemia, ATP-depleting ischemia)
• Pharmacologic targeting of troponin/tropomyosin system (e.g., cardiac troponin assays in MI) underscores medical importance

Key Terminology Recap

• Sarcomere, Z-line, Thick vs. Thin filament
• Myosin head, cross-bridge, power stroke
• Actin, tropomyosin, troponin (TnT, TnC, TnI)
• ATP ↔ ADP + P_i cycling
• Sarcoplasmic reticulum, \text{Ca^{2+}} release
• Sliding filament theory

Concept Integration / Take-Home Messages

• Contraction is a chemical-mechanical cycle requiring:
  1. Electrical signal → \text{Ca^{2+}} release
  2. Regulatory protein shift → binding site exposure
  3. ATP-powered myosin conformational changes → mechanical pull
• The synchronicity of millions of sarcomeres yields macroscopic muscle shortening & force generation