Muscle Tissue: Skeletal, Smooth, Cardiac — Comparison

1. Classification

• Skeletal — attached to bones, provides voluntary movement, posture, breathing.
• Cardiac — myocardium only; involuntary, rhythmic.
• Smooth — walls of blood vessels, GI tract, bronchi, uterus, eye (iris, ciliary muscle).
• Origin: skeletal — from somite myotomes (mesoderm); cardiac — from visceral mesoderm; smooth — from mesoderm (and ectoderm for the iris).

2. Comparative table

3. Skeletal muscle — structure

• Muscle fiber = syncytium (fusion of myoblasts) with hundreds of nuclei.
• Myofibrils consist of sarcomeres — the structural units of contraction (from Z-disc to Z-disc).
• Sarcomere: actin (thin filaments, I-band), myosin (thick filaments, A-band), M-line in the center, Z-disc (α-actinin).
• Regulatory proteins on actin: tropomyosin and troponin (Tn-I, Tn-T, Tn-C).
• Structural proteins: titin (spring from Z to M), nebulin, dystrophin (connection with sarcolemma).
• Sarcolemma → T-tubules → triad (T-tubule + 2 SR cisternae) → excitation-contraction coupling to the sarcoplasmic reticulum.

4. Contraction mechanism (skeletal)

• AP in motor nerve → ACh at neuromuscular junction → sarcolemma depolarization.
• T-tubules depolarization → DHP receptor → RyR1 on SR → Ca²⁺ release.
• Ca²⁺ → troponin C → tropomyosin displacement → actin sites open.
• Myosin head binds to actin → ATP hydrolysis → power stroke → filament sliding.
• New ATP detaches the head; cycle repeats as long as Ca²⁺ and ATP are present.
• Relaxation — SERCA pumps Ca²⁺ back into the SR.

5. Skeletal Muscle Fiber Types

• Type I (slow, red, oxidative) — myoglobin, high mitochondria content, aerobic metabolism; endurance (m. soleus).
• Type IIa (fast oxidative-glycolytic) — mixed metabolism.
• Type IIx (IIb in rodents) — fast glycolytic, white; short, powerful bursts.
• Ratio is genetically determined + trainable.

6. Cardiac Muscle

• Cardiomyocytes — mono-/binucleated, centrally located nucleus, branching.
• Intercalated discs contain: desmosomes (mechanical linkage), adhering junctions (fascia adherens — actin anchoring), gap junctions (connexin 43 — rapid electrical transmission).
• Automatism — in the sinoatrial node (If current via HCN channels, slow diastolic depolarization).
• Unlike skeletal muscle — prolonged plateau phase of the AP (L-type Ca²⁺), protecting against tetanus.
• Ca²⁺ for contraction: extracellular + triggered CICR (Ca-induced release via RyR2).
• Regeneration is almost absent; post-infarction — connective tissue scar.

7. Smooth Muscle

• Cells are spindle-shaped, 20–500 µm, with a single central nucleus.
• No sarcomeres or myofibrils; thin and thick filaments attach to dense bodies (analogous to Z-discs).
• Contraction: Ca²⁺ + calmodulin → MLCK (myosin light-chain kinase) activation → myosin phosphorylation → binding to actin.
• Relaxation: MLCP (phosphatase) dephosphorylates myosin.
• Modulation: Rho-kinase inhibits MLCP → increases Ca²⁺ sensitivity (crucial for vascular tone).
• Two types: unitary (visceral — syncytium with gap junctions; GI tract, uterus) and multi-unit (vessels, iris).
• Regeneration — good (including hyperplasia in the uterus during pregnancy).

8. Neuromuscular Junction

• Motor axon → terminal with synaptic vesicles (ACh).
• AP in the terminal → opening of Ca channels → exocytosis of ACh.
• ACh → nicotinic receptor (N-M, nAChR) on the end-plate → Na⁺/K⁺ → excitatory postsynaptic potential → AP.
• AChE in the cleft rapidly degrades ACh.
• Blockers: curare (competitive), succinylcholine (depolarizing), botulinum toxin (blocks ACh release), α-bungarotoxin.

9. Myopathies and Clinical Syndromes

• Duchenne muscular dystrophy (X-linked, Xp21, dystrophin-) — progressive weakness, calf pseudohypertrophy, positive Gowers' sign, ↑ CK.
• Becker muscular dystrophy — less severe, partial dystrophin deficiency.
• Myasthenia gravis — antibodies to nAChR → weakness, fluctuations, improves with rest; diagnostics: neostigmine test, ENMG decrement, mediastinal CT (thymoma).
• Lambert-Eaton syndrome — antibodies to presynaptic P/Q Ca²⁺ channels; often paraneoplastic (small cell lung cancer).
• Polymyositis/dermatomyositis — autoimmune inflammatory myopathies.
• Malignant hyperthermia — RYR1 mutation, triggered by halogenated anesthetics and succinylcholine; treatment — dantrolene.
• Rhabdomyolysis — skeletal muscle injury (trauma, ischemia, metabolic); myoglobinuria, AKI.

10. Energetics and Metabolism

• ATP: direct hydrolysis at the myosin head; muscle stores ~5 s of work.
• Creatine phosphate (CP): ATP regeneration, stores for ~10–15 s.
• Anaerobic glycolysis: in the absence of O₂, lactate, up to 1–2 min.
• Oxidative phosphorylation: prolonged work, in slow fibers.
• Myocardium — almost exclusively oxidative, utilizes fatty acids (70%), glucose, lactate.

11. Regeneration and Satellite Cells

• Satellite cells (Pax7+) lie between the sarcolemma and basement membrane — myogenic stem cells.
• Upon injury, they activate, divide, and fuse with the muscle fiber.
• Capacity declines with age (sarcopenia).
• Myocardium — minimal regeneration (~1%/year); primary outcome is scarring.
• Smooth muscle — good hyperplasia + hypertrophy.

12. FAQ

Why is skeletal muscle multinucleated?
It is formed by the fusion of many myoblasts into a single syncytium — a huge cytoplasm requires multiple nuclei for local protein synthesis.

Why can the heart not undergo tetanic contraction?
A long refractory period due to the AP plateau phase (L-type Ca²⁺ ~200 ms) — a new stimulus arrives when the muscle has already begun to relax, which is critical for the filling-ejection cycle.

What is the key regulatory difference between skeletal and smooth muscle?
In skeletal muscle, Ca²⁺ acts on troponin C (actin-dependent mechanism). In smooth muscle, via calmodulin, it activates MLCK, which phosphorylates myosin (myosin-dependent). Therefore, smooth muscle contraction is slower but more energy-efficient.

How to explain calf pseudohypertrophy in Duchenne?
True muscle fibers are replaced by adipose and connective tissue — calves visually appear well-developed, but lack strength. This is a sign of progressing dystrophy.

Why is botulinum toxin used both in treatment and as a poison?
It blocks ACh exocytosis at the neuromuscular junction. Therapeutically — microdoses for spasticity, blepharospasm, dystonias, wrinkles; in massive poisoning — flaccid paralysis, including respiratory paralysis.

See also: Action Potential · Myasthenia gravis · Cardiac cycle · Muscular dystrophies · Histology Catalog