Muscle Physiology: Skeletal, Cardiac & Smooth
A Step 1–focused muscle physiology lesson contrasting skeletal, cardiac, and smooth muscle across the cross-bridge cycle, the three EC-coupling wiring diagrams, and the length–tension/force–velocity curves, anchored by high-yield clinical correlations (malignant hyperthermia, digoxin inotropy, Duchenne). Emphasizes the tested numbers, transporters, and second-messenger contrasts.
The one pathway, three wiring diagrams
All three muscle types shorten by the same final common pathway — Ca²⁺ triggers an ATP-powered actin–myosin interaction — but they differ in where the Ca²⁺ comes from and what it binds. Striated muscle (skeletal + cardiac) is built from ordered sarcomeres and Ca²⁺ acts on troponin C; smooth muscle has no sarcomeres and no troponin, so Ca²⁺ acts on calmodulin.
Step 1 lives in the contrasts. Skeletal excitation–contraction (EC) coupling is a mechanical switch that needs no extracellular Ca²⁺; cardiac depends on calcium-induced calcium release and therefore does need extracellular Ca²⁺; smooth muscle is graded by a kinase (MLCK). Learn those three wiring diagrams and most muscle questions fall out.
Cross-bridge cycle (start in the rigor state, myosin bound to actin):
- ATP binds myosin → myosin releases actin.
- ATP hydrolysis (→ ADP + Pi) cocks the head to its high-energy position.
- With actin exposed (Ca²⁺ on troponin moved tropomyosin) → cross-bridge forms.
- Power stroke: Pi released → head pivots, pulling the thin filament toward the M-line; then ADP released.
- No new ATP → head stays locked = rigor.
- ATP is required to release myosin from actin (binding to actin does not need ATP) → basis of rigor mortis (post-mortem ATP depletion locks cross-bridges).
- Sliding filament: filaments slide, they don't shorten. During contraction the I band and H zone shrink and the sarcomere shortens; the A band stays constant (= thick-filament length).
- Skeletal: AP travels down the T-tubule → the DHP receptor acts as a voltage sensor → mechanically pulls open RyR1 on the SR → SR Ca²⁺ release. No extracellular Ca²⁺ required.
- Cardiac: AP plateau opens L-type Ca²⁺ channels (DHP receptors) → Ca²⁺ influx binds RyR2 → calcium-induced calcium release (CICR) from the SR. Requires extracellular Ca²⁺.
- Smooth: depolarization and/or Gq → IP₃ → Ca²⁺ (extracellular + SR) → Ca²⁺–calmodulin → activates MLCK → phosphorylates the myosin light chain → contraction. No troponin.
- Relaxation (striated): SERCA pumps Ca²⁺ back into the SR; cardiac also extrudes Ca²⁺ via the Na⁺/Ca²⁺ exchanger (NCX). Smooth muscle relaxes when myosin light-chain phosphatase (MLCP) dephosphorylates the light chain.
Skeletal vs cardiac vs smooth
| Feature | Skeletal | Cardiac | Smooth |
|---|---|---|---|
| Striations | Yes | Yes | No |
| Nuclei | Many, peripheral | 1–2, central | 1, central |
| Ca²⁺ binds | Troponin C | Troponin C | Calmodulin |
| Ca²⁺ source | SR only | SR + extracellular (CICR) | SR (IP₃) + extracellular |
| EC coupling | Mechanical (DHP ↔ RyR1) | CICR (DHP → Ca²⁺ → RyR2) | Ca²⁺–calmodulin → MLCK |
| T-tubules | Triads at A–I junction | Dyads at Z-line | None |
| Gap junctions | No | Yes (intercalated discs) | Yes (single-unit) |
| Pacemaker activity | No | Yes (SA node) | Some (slow waves) |
| Regeneration | Satellite cells (limited) | Minimal / none | Good |
A 19-year-old receives succinylcholine + sevoflurane for an appendectomy. Minutes later: masseter rigidity, a sharply rising end-tidal CO₂ (the earliest sign), tachycardia, generalized rigidity, and temperature climbing past 40 °C (a late sign).
- Mechanism: autosomal-dominant mutation in RYR1 (or CACNA1S/DHP) → volatile anesthetics and succinylcholine trigger uncontrolled SR Ca²⁺ release → sustained contraction → hypermetabolism, heat, hyperkalemia, and rhabdomyolysis (↑ CK, myoglobinuria) with mixed respiratory + metabolic acidosis.
- Treatment: dantrolene — a RyR1 antagonist that shuts off SR Ca²⁺ release (also used for neuroleptic malignant syndrome). Stop the trigger agent, cool, and correct hyperkalemia.
A patient with systolic heart failure improves on digoxin.
- Mechanism: digoxin inhibits Na⁺/K⁺-ATPase → intracellular Na⁺ rises → the Na⁺/Ca²⁺ exchanger loses its driving gradient and extrudes less Ca²⁺ → intracellular and SR Ca²⁺ rise → ↑ contractility (positive inotrope). It also raises vagal tone (slows AV conduction).
- Trap: hypokalemia potentiates toxicity — K⁺ and digoxin compete for the same site on the pump, so low K⁺ increases digoxin binding.
Structural contrast — Duchenne muscular dystrophy: an X-linked frameshift (out-of-frame) mutation in dystrophin unanchors the sarcolemma from the cytoskeleton → membrane tears, Ca²⁺ influx, and progressive fiber death (markedly ↑ CK, calf pseudohypertrophy). Here the contractile machinery is intact — the membrane scaffold fails.
The two curves: length–tension & force–velocity
Length–tension: active tension is maximal at the optimal sarcomere length (~2.0–2.2 µm), where thick–thin overlap maximizes available cross-bridges. Over-shortened (filaments collide) or over-stretched (too few cross-bridges) sarcomeres generate less active force; total tension also includes a passive component that rises with stretch.
In the heart this is the Frank–Starling relationship: ↑ preload (end-diastolic volume) stretches sarcomeres toward optimal overlap → ↑ stroke volume — how the ventricle matches output to venous return.
Force–velocity is inverse: the greater the afterload, the slower the shortening velocity; Vmax occurs at zero load, and ↑ contractility shifts the curve up and to the right (raising both Vmax and maximal force).
Smooth-muscle tone: second messengers (and the cardiac twist)
| Signal / messenger | Pathway | Smooth-muscle effect | Example |
|---|---|---|---|
| Gq / IP₃ | ↑ cytosolic Ca²⁺ → Ca–calmodulin → MLCK | Contraction | α₁ vasoconstriction, M₃ |
| RhoA / Rho-kinase | inhibits MLCP (Ca²⁺ sensitization) | Contraction (sustained) | vascular tone, latch state |
| NO → cGMP (PKG) | ↓ Ca²⁺, activates MLCP | Relaxation | nitrates, EDRF vasodilation |
| cAMP (PKA) | inhibits MLCK | Relaxation | β₂ → bronchodilation |
- Sarcomere bands: the A band is Always the sAme length; the H zone and I band shrink during contraction (H and I get smaller).
- Smooth = the M's: sMooth Muscle uses calModulin + MLCK (no troponin).
- Dantrolene damps the Ryanodine receptor → stops SR Ca²⁺ release in malignant hyperthermia (and NMS).
- Rigor = no ATP, no release — myosin needs ATP to let go of actin.
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