---

Muscle Physiology - Overview

The Three Muscle Types

---

1. Skeletal Muscle

Structure

• Organized into motor units: one alpha-motor neuron + all muscle fibers it innervates
• Small/precise muscles (e.g., extraocular) have <5 fibers/unit; large muscles (e.g., gastrocnemius) have up to 1800 fibers/unit
• Fibers contain actin (thin) and myosin (thick) filaments arranged in sarcomeres

Neuromuscular Junction (NMJ)

1. Action potential reaches the motor axon terminal
2. Acetylcholine (ACh) is released from presynaptic vesicles into the synaptic cleft (~50 nm wide)
3. ACh binds to nicotinic receptors on the sarcolemma → depolarization → muscle action potential

Excitation-Contraction (E-C) Coupling

1. Action potential propagates along the sarcolemma and into T-tubules
2. T-tubule depolarization triggers a conformational change in dihydropyridine receptors (DHPR) - voltage sensors
3. DHPR mechanically opens ryanodine receptors on the sarcoplasmic reticulum (SR) → Ca²⁺ floods the cytoplasm (from <10⁻⁷ M to 10⁻⁶ M)
4. Ca²⁺ binds troponin C on the thin filament (up to 4 ions/molecule, cooperative binding)
5. Troponin conformational change moves tropomyosin off the myosin-binding sites on actin
6. Myosin heads bind actin → ATP hydrolysis → power stroke (actin slides toward the center of the sarcomere)
7. Relaxation: SR Ca²⁺-ATPase pumps Ca²⁺ back into the SR; tropomyosin re-blocks actin

Fiber Types

Types of Contraction

Eccentric contractions produce the greatest tension and carry the highest injury risk.

Key Clinical Points

• Myasthenia gravis: IgG antibodies against ACh receptors → fatigable weakness, ptosis, diplopia
• Botulinum toxin: blocks presynaptic ACh release (used for spasticity in cerebral palsy)
• Succinylcholine: depolarizing neuromuscular blocker (short-acting)
• Curare/vecuronium: non-depolarizing blockers, reversed by anticholinesterases (neostigmine)

---

2. Cardiac Muscle

• Striated, like skeletal muscle, with the same actin/myosin sliding filament mechanism
• Fibers are arranged as a functional syncytium - cells connected by intercalated discs containing gap junctions that allow rapid ion diffusion and electrical coupling
• Three types: atrial, ventricular, and specialized conductive fibers (SA/AV node, Purkinje)
• Left ventricular fibers are arranged in a double helix, producing a twisting (torsion) motion during systole - the apex rotates counterclockwise while the base rotates clockwise
• Key difference from skeletal muscle: Ca²⁺ entry from outside the cell (via L-type channels) is required to trigger SR Ca²⁺ release (calcium-induced calcium release, CICR) - this does NOT occur in skeletal muscle
• Action potential has a prolonged plateau phase (phase 2) due to L-type Ca²⁺ channel inflow, which extends the refractory period and prevents tetany

---

3. Smooth Muscle

• No sarcomeres; no troponin - instead uses calmodulin to regulate contraction
• Contraction mechanism: Ca²⁺ → binds calmodulin → activates myosin light-chain kinase (MLCK) → phosphorylates myosin → cross-bridge cycling
• Slow cross-bridge cycling: 1/10 to 1/300 the rate of skeletal muscle
• Despite this, maximum force can be 4-6 kg/cm² (greater than skeletal muscle's 3-4 kg/cm²) due to prolonged cross-bridge attachment time
• Energy efficient: requires only 1/10 to 1/300 the energy to maintain the same tension
• Latch mechanism: smooth muscle can maintain sustained tonic contraction for hours at minimal energy cost by keeping cross-bridges "locked" in the attached state
• Total contraction time is ~30x longer than a single skeletal muscle twitch (1-3 seconds vs. ~50-100 ms)
• Triggered by: stretch, hormones (e.g., oxytocin, norepinephrine), autonomic nerves, local metabolites

---

Quick Comparison Summary

---