Physiology of Muscles
Physiology of Muscles
What You'll Learn
- Sarcomere anatomy — A-band (dark, myosin), I-band (light, actin only), H-zone (myosin only), Z-line (sarcomere boundary), M-line (center)
- Excitation-contraction coupling — AP → T-tubule → DHP receptor → RyR → Ca²⁺ release → troponin C binding → cross-bridge cycling
- Fiber types — Type I (slow, oxidative, red, fatigue-resistant) vs Type II (fast, glycolytic, white, fatigable)
- Motor unit — Henneman size principle: small motor neurons recruited first
- Metabolic myopathies — McArdle (myophosphorylase, second wind), Pompe (acid maltase, respiratory failure), CPT II (recurrent rhabdomyolysis)
- Myopathic vs neuropathic patterns — proximal vs distal weakness, EMG and biopsy distinctions
- Key dystrophies — DMD/BMD (dystrophin), DM1 vs DM2, FSHD, LGMD
- Biopsy patterns — ragged red fibers (mito), rimmed vacuoles (IBM), perifascicular atrophy (DM), fiber type grouping (reinnervation)
HighYield Pearls
- A-band stays constant: During contraction the I-band & H-zone shorten as Z-lines approach — the A-band length is unchanged. Single most-tested sarcomere fact.
- DHPR ↔ RYR1 mechanical coupling: Skeletal EC coupling does NOT require extracellular Ca²⁺ influx — T-tubule DHPR (voltage sensor) directly opens RYR1 on SR. Cardiac (RYR2) uses Ca-induced Ca release.
- Rigor mortis = no ATP: Myosin needs ATP to DETACH from actin (not to bind). Loss of ATP after death locks cross-bridges.
- Henneman size principle: Smallest (Type I, low-threshold) motor units recruited first; largest (Type IIx/b) last as force demand ↑.
- Malignant hyperthermia: RYR1 (or CACNA1S) gain-of-function + volatile anesthetic / succinylcholine → masseter spasm, hyperthermia, rhabdo, hyperkalemia. Treat with dantrolene + cooling.
- Type II atrophy = disuse / steroid / endocrine: Steroid myopathy, Cushing, hyperthyroid, paraneoplastic & disuse selectively atrophy Type II fibers (proximal, painless, normal CK).
- Fiber type grouping = reinnervation: Loss of normal mosaic checkerboard on ATPase stain = chronic neurogenic process (axonal sprouting from surviving motor neurons).
- Metabolic myopathy red flags: Exercise-induced cramps + myoglobinuria → think McArdle (PYGM, “second wind”), CPT-II (long exercise/fasting, adult rhabdo), or MH-spectrum (RYR1).
- Neonatal AChR γ → ε switch: Fetal γ-subunit replaced by adult ε-subunit perinatally — relevant to slow-channel/fast-channel congenital myasthenic syndromes.
- Dystroglycan complex links cytoskeleton to ECM: Dystrophin → β-dystroglycan → α-dystroglycan → laminin. Disruption → DMD/BMD, LGMD, dystroglycanopathies (Walker-Warburg, MEB, FCMD).
🔍 Quick ReferenceStructure / EC coupling · Fiber types / metabolism · Disease / drug
Structure / EC coupling
- Z-line α-actinin → anchors thin (actin) filaments — sarcomere boundary
- M-line myomesin → anchors thick (myosin) filaments at sarcomere center
- A-band unchanged, I/H shrink → sliding filament theory (contraction)
- Troponin C binds Ca²⁺ → tropomyosin shift → exposes actin myosin-binding sites
- DHPR (CACNA1S, L-type) → T-tubule voltage sensor mechanically gates RYR1
- RYR1 on SR → Ca²⁺ release channel for skeletal EC coupling (RYR2 = cardiac)
- SERCA + phospholamban → pumps Ca²⁺ back into SR (relaxation)
- Myosin ATPase → powers cross-bridge cycle; ATP needed to DETACH (rigor if absent)
Fiber types / metabolism
- Type I — slow oxidative, red → high myoglobin/mitochondria, fatigue-resistant, postural, MyHC-I
- Type IIa — fast oxidative-glycolytic, pink → moderate fatigue, MyHC-IIa
- Type IIx/IIb — fast glycolytic, white → anaerobic, high force, rapid fatigue, sprinting
- ATPase pH 9.4 dark → Type II (reversed at pH 4.3 → Type I dark)
- SDH / NADH-TR dark → Type I (mitochondria-rich) on oxidative stains
- Henneman size principle → small motor units recruited first; rate coding modulates force
- Creatine phosphate & creatine kinase → immediate ATP buffer (first ~10 sec)
- Carnitine palmitoyl shuttle → imports long-chain fatty acyl-CoA into mitochondria for β-oxidation
- Satellite cells (Pax7+) → quiescent muscle stem cells under basal lamina; MyoD activation → regeneration
Disease / drug association
- Malignant hyperthermia → RYR1 / CACNA1S + volatiles / succinylcholine → dantrolene
- Central core disease → RYR1 congenital myopathy + MH susceptibility
- Caffeine-halothane contracture test → gold-standard MH susceptibility screen
- McArdle disease → PYGM (myophosphorylase) deficiency, “second wind” phenomenon, flat lactate on ischemic forearm test
- CPT-II deficiency (adult) → exercise/fasting-induced rhabdomyolysis & myoglobinuria
- Rhabdomyolysis labs → CK ≥ 5× ULN, myoglobinuria, hyperK, hyperphos, HYPOcalcemia, AKI, ↑ uric acid
- Ragged-red & COX-negative fibers → mitochondrial myopathy (oxidative phosphorylation failure)
- Fiber type grouping + angulated fibers → chronic neurogenic reinnervation
- Selective Type II atrophy → steroid / disuse / thyrotoxic / Cushing / paraneoplastic myopathy
- Dystrophin / dystroglycan / sarcoglycan loss → DMD & BMD / dystroglycanopathy / LGMD
- Neonatal γ → ε AChR subunit switch → relevant to congenital myasthenic syndromes (slow/fast channel)
Muscle Fiber Structure
Sarcomere Anatomy
The sarcomere is the basic contractile unit, bounded by two Z-lines.
| Structure | Location | Composition | Board-Relevant Detail |
|---|---|---|---|
| A-band | Center of sarcomere | Thick (myosin) +/- overlapping thin filaments | Does NOT change length during contraction (Anisotropic, dArk). Memory aid: A-band = Always the same length — the single most tested sarcomere fact. |
| I-band | Between A-bands of adjacent sarcomeres | Thin filaments only (actin) | Shortens during contraction (Isotropic, lIght) |
| H-zone | Center of A-band | Myosin only (no actin overlap) | Shortens during contraction; disappears at full contraction |
| Z-line (Z-disc) | Sarcomere boundary | Alpha-actinin anchors actin | Defines sarcomere; Z-to-Z = one sarcomere |
| M-line | Center of H-zone | Myomesin; anchors myosin | Middle of sarcomere |
Board Pearl
During contraction, the A-band stays the same length. The I-band and H-zone shorten as actin slides over myosin (sliding filament theory). This is the most commonly tested sarcomere fact.
Thick vs Thin Filaments
| Filament | Main Protein | Associated Proteins | Function |
|---|---|---|---|
| Thick | Myosin (heavy chains) | Myosin light chains; titin spans Z-line to M-line (third filament system); provides passive elasticity, anchors thick filament, mechanosensing. (Largest known protein.) | Cross-bridge formation; ATPase activity in myosin head |
| Thin | Actin (F-actin polymer) | Tropomyosin, Troponin complex (T, C, I) | Troponin C binds Ca²⁺ → tropomyosin shifts → exposes myosin-binding site |
Troponin Subunits
- Troponin C — binds Calcium (the Ca²⁺ sensor)
- Troponin T — binds Tropomyosin (attaches complex to thin filament)
- Troponin I — Inhibits actin-myosin interaction (holds tropomyosin in blocking position)
T-Tubules and Sarcoplasmic Reticulum
- T-tubules (transverse tubules) — invaginations of the sarcolemma that carry the action potential deep into the muscle fiber
- Sarcoplasmic reticulum (SR) — intracellular Ca²⁺ store; terminal cisternae flank T-tubules forming the triad
- Triad = 1 T-tubule + 2 terminal cisternae (located at the A-I band junction in skeletal muscle)
- DHP receptor (dihydropyridine receptor) — voltage sensor on T-tubule membrane
- RyR1 (ryanodine receptor) — Ca²⁺ release channel on SR; mechanically coupled to DHP receptor in skeletal muscle
Board Pearl
Malignant hyperthermia results from a mutation in the RyR1 gene (less commonly CACNA1S, DHPR α1 subunit) → uncontrolled Ca²⁺ release from SR → sustained contraction, hyperthermia, rhabdomyolysis. Triggered by volatile anesthetics and succinylcholine. Treat with dantrolene (blocks RyR1).
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