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Physiology 3% exam weight

Nerve & Muscle

Part of the INI CET (AIIMS PG) study roadmap. Physiology topic physio-003 of Physiology.

Muscle Physiology: Skeletal Muscle Contraction covers skeletal muscle contraction for INI CET (AIIMS PG).

Muscle Architecture:

  • Sarcomere: Basic contractile unit — Z-disc to Z-disc
    • A-band: Myosin (thick) filaments — length constant during contraction
    • I-band: Actin (thin) filaments only — shortens during contraction
    • H-zone: Myosin only (center of A-band) — shortens during contraction
    • Z-disc: Anchors actin filaments; moves closer during contraction
    • M-line: Center of sarcomere; holds myosin in register
  • Sarcoplasmic Reticulum (SR): Ca²⁺ storage; wraps around myofibrils; terminal cisternae (coupled to T-tubules at triad)

Molecular Mechanism (Sliding Filament Theory):

  1. AP in muscle fiber: T-tubule → DHPR (dihydropyridine receptor — L-type Ca²⁺ channel) → activates ryanodine receptor (RYR1) on SR → Ca²⁺ release
  2. Cross-bridge cycle:
    • Ca²⁺ binds troponin C → tropomyosin shifts → myosin-binding sites on actin exposed
    • Myosin head binds actin (strong binding in ADP + Pi state)
    • Power stroke: Pi and ADP released → myosin head pivots → actin filament slides toward M-line (7-9 nm stroke)
    • New ATP binds myosin → myosin dissociates from actin
    • ATP hydrolysis → myosin head returns to cocked position
  3. Relaxation: Ca²⁺-ATPase (SERCA) pumps Ca²⁺ back into SR → Ca²⁺ dissociates from troponin → tropomyosin blocks myosin-binding sites

Excitation-Contraction Coupling:

  • Motor neuron AP → ACh release at NMJ → muscle fiber depolarization
  • Depolarization spreads across sarcolemma → down T-tubules
  • Triad: T-tubule (with DHPR) + junctional SR (with RYR) + terminal cisternae
  • DHPR mechanically opens RYR1 → Ca²⁺ release (footplate model)

Mechanics:

  • Twitch: Single stimulus → single contraction-relaxation cycle
    • Latent period: 5–10 ms (excitation-contraction coupling)
    • Contraction time: 20–80 ms
    • Relaxation time: 20–100 ms
  • Isotonic vs Isometric: Isotonic (load constant, muscle changes length); Isometric (length constant, tension develops)
  • Length-tension relationship: Optimal overlap at sarcomere length ~2.0–2.2 μm; either stretched or shortened → reduced tension
  • Force-velocity relationship: As load decreases, velocity of shortening increases (Hill’s equation)

Muscle Fiber Types:

TypeColorMetabolismtwitchExample
Type I (slow oxidative)RedAerobic, many mitochondriaSlow, fatigue-resistantPostural muscles
Type IIa (fast oxidative)RedAerobic + anaerobicFast, fatigue-resistantPostural + phasic
Type IIb/IIx (fast glycolytic)WhiteAnaerobic (glycolysis)Fast, fatigableRapid movement

NMJ Physiology:

  • Motor end plate = specialized postsynaptic region
  • Miniature end plate potentials (MEPPs): Spontaneous quantal release of ACh (one vesicle)
  • EPP (End Plate Potential): Sum of ~200 MEPPs → reaches threshold → muscle AP
  • Safety factor: EPP always > threshold; ensures reliable transmission
  • Denervation: Supersensitivity (upregulation of ACh receptors — spreads beyond motor end plate)

Exam Tip for INI CET (AIIMS PG): Myasthenia gravis = autoimmune antibodies against ACh receptors (postsynaptic) → fatigable weakness (worse with repeated use) → treat with AChE inhibitors (pyridostigmine). Lambert-Eaton myasthenic syndrome = antibodies against presynaptic voltage-gated Ca²⁺ channels → weakness + autonomic dysfunction; reflexes improve after exercise (facilitation).