Skeletal Muscle Contraction

Muscle Microanatomy - Tiny Titans

• Sarcomere: Functional unit of muscle fiber (Z-line to Z-line). 📌 Mnemonic: "ZIAH M" (Z-disc, I-band, A-band, H-zone, M-line from edge to center).
  • Z-disc: Defines sarcomere boundaries; anchors thin filaments.
  • I-band: (Isotropic) Actin only; light band. Shortens during contraction.
  • A-band: (Anisotropic) Myosin ± actin overlap; dark band. Length remains constant.
  • H-zone: (Heller = bright) Myosin only; center of A-band. Shortens/disappears.
  • M-line: Midpoint of sarcomere; supports thick filaments.
• Filaments:
  • Thick Filaments: Primarily Myosin; heads possess ATPase activity and bind to actin.
  • Thin Filaments:
    • Actin: Globular (G-actin) polymerizes to filamentous (F-actin); contains myosin-binding sites.
    • Tropomyosin: Filamentous protein; covers myosin-binding sites on actin in resting muscle.
    • Troponin Complex: Regulatory protein.
      • Troponin C (TnC): Binds $Ca^{2+}$.
      • Troponin T (TnT): Binds to tropomyosin.
      • Troponin I (TnI): Inhibits actin-myosin interaction.

⭐ During muscle contraction, the A-band (myosin filament length) remains unchanged, while the I-band and H-zone shorten as Z-discs are pulled closer together.

NMJ & Excitation - Sparking Action

• Nerve AP at axon terminal → opens voltage-gated $Ca^{2+}$ channels → $Ca^{2+}$ influx.
• $Ca^{2+}$ triggers Acetylcholine (ACh) vesicle exocytosis into synaptic cleft.
• ACh binds nicotinic ACh Receptors (nAChR) on Motor End Plate (MEP).
• nAChR activation → ↑ $Na^+$ influx > ↑ $K^+$ efflux → graded End Plate Potential (EPP).
• If EPP reaches threshold (e.g., -50mV), muscle Action Potential (AP) generated.
• Muscle AP propagates along sarcolemma & invades T-tubules, initiating contraction.
• ACh rapidly degraded by Acetylcholinesterase (AChE) in cleft, terminating signal.

⭐ Myasthenia Gravis: Autoantibodies target nAChRs, ↓ EPP amplitude → muscle weakness, fatigue.

E-C Coupling - Calcium's Cue

• Excitation-Contraction (E-C) coupling: The physiological process linking sarcolemmal action potential (AP) to $Ca^{2+}$ release from SR, initiating muscle contraction.

• Key Players & Process:

• T-tubules: Invaginations of sarcolemma; transmit AP deep into muscle fiber near SR.

• DHPR (L-type $Ca^{2+}$ channel): Voltage sensor in T-tubule membrane.

• RyR1 (Ryanodine Receptor): SR $Ca^{2+}$ release channel; mechanically coupled to DHPR in skeletal muscle.

• Sarcoplasmic Reticulum (SR): Main intracellular $Ca^{2+}$ store in muscle cells.

⭐ In skeletal muscle, DHPR-RyR1 coupling is direct mechanical; calcium influx via DHPR is NOT needed for RyR1 opening (key difference from cardiac muscle).

Cross-Bridge & Sliding - Power Stroke Dance

• Sliding Filament Theory: Myosin heads pull actin filaments, shortening sarcomeres. H & I bands shorten; A band constant.

• Cross-Bridge Cycle:

• ATP Roles:
  • Energizes myosin (hydrolysis: $ATP \rightarrow ADP + P_i$).
  • Detaches myosin from actin.
  • Fuels Ca²⁺ pump (SERCA) for relaxation.

⭐ Rigor mortis: Post-mortem muscle stiffness due to ATP depletion; myosin can't detach from actin.

High‑Yield Points - ⚡ Biggest Takeaways

• EC Coupling: DHPR (T-tubule) activates RyR1 (SR) releasing Ca²⁺.
• Sliding Filaments: Actin & myosin slide; sarcomere shortens. A-band constant; I-band, H-zone shorten.
• Ca²⁺ Role: Binds Troponin C, moves tropomyosin, uncovers actin's myosin-binding sites.
• Cross-Bridge Cycle: ATP powers myosin attachment, power stroke, detachment.
• Rigor Mortis: No ATP means myosin stays bound to actin.
• Motor Unit: Single α-motor neuron + all fibers it innervates.
• Tetanus: Summation of twitches from high-frequency stimuli; sustained Ca²⁺.