Muscle organization (big → small)
Muscle → fascicle → muscle fiber (cell) → myofibrils → sarcomeres (Z-line to Z-line).
A sarcomere is the functional contractile unit.
Sarcomere anatomy & banding
• Z-line/disc: anchors thin filaments (actin).
• I-band: light band — only thin filaments; crosses Z-line.
• A-band: dark band — thick filaments (myosin) and overlap; stays same width during
contraction.
• H-zone: center of A-band with only thick filament (shrinks during contraction).
• M-line: center where thick filaments anchor.
Main molecular players
• Actin (thin filament): F-actin helix of G-actin monomers; each monomer has a myosin-
binding site.
• Myosin II (thick filament): tails form the filament, heads project outward (bind actin &
ATP).
• Tropomyosin: grooves along actin that block myosin-binding sites at rest.
• Troponin complex: TnC (binds Ca²⁺), TnI (inhibits binding), TnT (binds tropomyosin).
• Sarcoplasmic reticulum (SR): stores Ca²⁺.
• T-tubules: invaginations of sarcolemma that carry APs deep into the fiber.
• SERCA pumps: ATP-dependent pumps that return Ca²⁺ to SR for relaxation.
1) Motor neuron activation
• Motor neuron fires an action potential that travels to the neuromuscular junction (NMJ).
2) Neurotransmitter release & sarcolemma depolarization
• Presynaptic terminal releases acetylcholine (ACh).
• ACh binds nicotinic receptors on sarcolemma → opens Na⁺ channels → muscle action
potential.
3) Action potential propagation
• AP spreads across sarcolemma and down T-tubules, reaching interior and all sarcomeres.
4) Calcium release
• Voltage sensors (DHPR) in T-tubules mechanically couple to ryanodine receptors
(RyR) on SR → SR releases Ca²⁺ into sarcoplasm.
5) Regulatory shift — exposing binding sites
• Ca²⁺ binds troponin C → troponin changes conformation → tropomyosin shifts off
actin’s myosin-binding sites.
• At rest: tropomyosin blocks sites → OFF position. When Ca²⁺ binds: ON position
(binding sites exposed).
6) Cross-bridge cycle (repeat for force)
Each myosin head cycles through four main events (mnemonic: A-P-R-C — Attach, Pull,
Release, Cock):
a. Attach (cross-bridge formation)
• Myosin head (high-energy conformation; ADP + Pi bound) binds exposed site on
actin.
b. Power stroke (pulling)
• Release of Pi triggers the myosin head to pivot — the power stroke — pulling actin
toward the M-line. ADP is released during/after the stroke. This shortens the
sarcomere (Z-lines move closer).
c. Release (detachment)
• ATP binds to myosin head → myosin releases actin.
d. Re-cock (recovery stroke)
• ATP is hydrolysed (ATP → ADP + Pi) by myosin ATPase; the released energy
returns the myosin head to its high-energy (cocked) position, ready for another
attachment if Ca²⁺ is still present.
• Note: Myosin acts as an ATPase enzyme — hydrolyses ATP to power movement.
7) Many cycles → macroscopic shortening
• Thousands of myosin heads cycle asynchronously → smooth, steady contraction. I-bands
and H-zone narrow; A-band constant.
8) Relaxation (termination)
• Motor neuron stops firing → no more ACh → muscle APs cease.
• SERCA pumps use ATP to resequester Ca²⁺ into SR → cytosolic Ca²⁺ falls.
• Troponin releases Ca²⁺ → tropomyosin re-blocks binding sites → cross-bridges cannot
form → muscle relaxes.
• Without ATP (e.g., after death) myosin cannot detach → rigor.
Energetics — ATP & sources
• ATP required for: detachment of myosin from actin, re-cocking myosin, SERCA Ca²⁺
reuptake, Na⁺/K⁺ pumps.
• Sources: direct ATP (seconds), creatine phosphate (very rapid), anaerobic glycolysis
(short bursts), oxidative phosphorylation (sustained, requires O₂).
• Muscles have many mitochondria for sustained work.