EW

lecture 3 muscle physiology part 2

Overview of the Sarcomere

  • Fundamental contractile unit within a myofibril of skeletal muscle.
  • Extends from one Z disc (also called Z line) to the next Z disc.
  • Contains two primary types of protein filaments:
    • Thick filaments (myosin)
    • Thin filaments (actin)
  • Arrangement produces the light‐and‐dark striations seen under the microscope.

Thick vs. Thin Filaments

  • Thick Filaments (Myosin)
    • Comprised of hundreds of myosin molecules bundled together → appear “thick.”
    • Each myosin molecule has:
    • Tail: forms the core of the thick filament.
    • Head (cross‐bridge): protrudes outward; possesses ATPase activity and binding site for actin.
    • Heads project radially, allowing interaction with nearby thin filaments.
  • Thin Filaments (Actin)
    • Built from two intertwined strands of G-actin; each G-actin bears a myosin-binding site.
    • Regulatory proteins associated with thin filaments:
    • Tropomyosin: long, rope-like molecule that lies in the groove of the actin helix, physically covering myosin-binding sites.
    • Troponin: globular complex that anchors tropomyosin; serves as Ca^{2+} sensor (binds Ca^{2+}, triggering conformational change that exposes binding sites).
  • Color coding used in lecture illustrations (may vary by slide):
    • Thick filaments: red or pink.
    • Thin filaments: yellow or blue.

Banding Pattern & Landmarks

  • I Band (Isotropic / Light Band)
    • Contains only thin filaments (actin).
    • Bisected by the Z disc.
  • A Band (Anisotropic / Dark Band)
    • Length of the thick filament; encompasses areas with and without overlap.
    • Sub-regions:
    • Zone of overlap: peripheral regions where thick and thin filaments interdigitate.
    • H Zone: central lighter stripe of A band that contains thick filaments only (no actin overlap).
    • M Line: protein complex at the center of the H zone; aligns thick filaments ("M" for middle).
  • Z Disc / Z Line
    • Zig-zag line of protein anchoring thin filaments; defines sarcomere boundaries.

Sliding Filament Theory (Qualitative Summary)

  • During contraction, myosin heads cyclically bind to actin, pivot, and pull thin filaments toward the M line.
  • Outcomes observable in a microscope:
    1. Zone of overlap enlarges.
    2. I band narrows.
    3. H zone may disappear at maximal shortening.
    4. A band length remains constant (thick filaments do not change length).
  • Overall sarcomere (and hence muscle fiber) length can decrease by up to 30\%.

Ancillary / Structural Proteins

  • Dystrophin: links sarcomere to cell membrane; transmits force laterally to extracellular matrix.
  • Titin: massive elastic protein; spans from Z disc to M line, centering thick filament & providing recoil.
  • Nebulin: runs alongside thin filament; acts as a molecular ruler for actin length.
  • Myomesin: forms the M line; stabilizes thick filament arrangement.
  • α-Actinin: principal constituent of the Z disc anchoring actin filaments.

Hierarchical Organization of Skeletal Muscle (Macro → Micro)

  1. Whole Muscle
    • Encased by epimysium; connects to bone via tendon (continuous with periosteum).
  2. Fascicle
    • Bundle of muscle fibers; wrapped by perimysium.
  3. Muscle Fiber (Cell)
    • Surrounded by endomysium + plasma membrane (sarcolemma).
    • Multinucleated; abundant mitochondria for ATP supply.
    • Invaginations of sarcolemma form T tubules (conduct action potentials & distribute Na^{+} / depolarization).
    • Internal Ca^{2+} reservoir: sarcoplasmic reticulum (SR) surrounds each myofibril.
  4. Myofibril
    • Cylindrical bundle of repeating sarcomeres; occupies most cytoplasmic volume.
  5. Sarcomere (smallest contractile unit)
    • Bounded by Z discs; contains thick & thin filaments arranged in precise lattice.

Contraction & Relaxation (Functional Recap)

  • Contraction phase
    • Myosin pulls on actin → thin filaments slide inward → Z discs move closer.
    • Structural proteins (titin, dystrophin, etc.) distribute and coordinate force so the entire fiber—and ultimately the muscle—shortens.
  • Relaxation phase
    • Ca^{2+} is pumped back into SR; troponin–tropomyosin complex re-covers binding sites → cross-bridges detach; sarcomere returns toward resting length (with aid of titin’s elasticity & external forces).

Microscopic Visualization Correlates

  • Transmission electron micrographs at \sim 20{,}000\times magnification confirm:
    • Alternating I (light) and A (dark) bands.
    • Zig-zag Z discs within I bands.
    • Central H zone & M line inside each A band.
    • Increased density where actin & myosin overlap (darker tone in overlap regions).

Key Take-Home Points

  • Remember the mnemonic “MATH TT” for core players:
    • Myosin → thick filament, motor heads.
    • Actin → thin filament, binding sites.
    • Tropomyosin → covers sites.
    • Troponin → tethers tropomyosin & binds Ca^{2+}.
  • Band names: I band = lIght, A band = dArk; H zone = tHick only; M line = Middle; Z disc = border.
  • Sliding filament theory explains how filament lengths stay constant yet sarcomere shortens by up to 30\% via increased overlap.