04b - Skeletal Muscle Structure

skeletal muscle function

1. facilitate voluntary movement of bones underlying locomotion and work production

2. controls breathing of lungs via contraction of diaphragm

3. controls voluntary movement of tongue

4. functions as pump to assist return or venous blood supply to heart

origin vs insertion

skeletal muscle attaches to skeleton by way of tendons and typically spans a joint

• origin: proximal part of attachment of tendon

• insertion: distal point of attachment of tendon

  • close to joint to allow broad range of motion

muscle organization

1. fasciculus: bundle of muscle fibers

2. muscle fibers: individual muscle cell containing bundle of myofibrils

3. myofibril: specialized muscle cytoskeletal structure composed of numerous overlapping filaments of actin and myosin

4. sarcomere: basic repeating unit of myofibril

5. myofilaments

muscle cell development

satellite cells (stem cells) → myoblast → myocyte → myotube → myofiber

sarcomere

basic repeating unit of myofibrils

• muscle contraction of actin over myosin filaments within individual sarcomeres

• A-band: overlap of thin and thick filaments

  • does not change during contraction

• I-band: thin filaments only

  • determines if muscle is contracted (short) or relaxed (long) based on width

• made of actin-containing thin chain, myosin-containing thick chain, nebulin filaments, and titin filaments

myosin-containing thick filaments

made of myosin heavy chain and myosin light chain

• heavy chain: contains dimerized tail that forms a rod-like alpha-helical coil and globular head domain that catalyzes hydrolysis of ATP and interacts with actin

• light chain → wraps around neck of myosin heavy chain to regulate availability of myosin to associate with actin

actin-containing thin filament

made of actin, tropomyosin, and troponin

• actin: globular protein assembled into long filamentous strands that coil together in pairs

• tropomyosin: rope-like molecule strung head-to-tail to form continuous chain that wraps around actin filament and also binds to troponin complex

• troponin: gropu of three proteins

  • TnT → attaches tropomyosin

  • TnC → sequesters calcium ions

  • TnI → acts as inhibitor of actin binding

  • influx of calcium causes conformational change that exposes myosin-binding site on actin

• tropomodulin: actin filament capping protein that binds actin, tropomyosin, and nebulin at pointed end of thin filament to regulate actin length

nebulin filament

part of sarcomere and made of large proteins whose filaments lie adjacent and bind to actin

• extends from end of thin filament to Z-lines, binding as many as 200 monomers of actin per molecule

• assists in regulating thin filament length

• contributes to structural integrity of myofibril by cross-linking filaments from adjacent sarcomeres

titin filaments

part of sarcomere and made of titin, the largest protein known to exist

• N-terminus ends from adjacent sarcomere overlap in z-line

• C-terminus ends overlap adjacent titin molecules in M-line to form continuous filament system

• domain in I-band provides elasticity to protein, giving mechanical resiliency

• contains extensive repeating motif structure that aSsists early assembly of myofibrils

• interaction with sarcomeric and regulatory components allow proteins to act as sarcomeric template and stabilizer

Z-line

defines lateral boundaries of sarcomere and constitutes anchoring site for thin, titin, and nebulin filaments

• alpha-actinin: major component that cross-links actin and titin filaments to provide structure to sarcomeres

M-line

middle of sarcomere and acts as the anchoring site for thick filaments

• myomesin: binds titin and myosin that plays a role in integrating thick filaments into assembling sarcomeres

• M-protein: interacts with titin and helps stabilize 3D arrangement of proteins within M-band

myosin-binding protein C (MyBP-C)

binds thick and thin filaments

• structural support for myosin organization in A-band to prevent filament from being too short

• cross-links myosin and titin to align myosin evenly for consistent and precise length across all sarcomeres

• regulates contraction by modulating ease of myosin heads attaching to actin

  • regulated by phosphorylation, speeding up cross-bridge formation when phosphorylated

costamere

specialized protein complexes within sarcolemma that anchors myofibrils circumferentially along long axis of mature skeletal and cardiac muscle cell

• secured to myofibrils by linkage to intermediate filaments that attach to Z-line of individual sarcomeres

• functions:

  • keep sarcolemma aligned and in register with contractile apparatus

  • protect sarcolemma against contraction-induced damage

  • transmit some of contraction forces laterally to extracellular matrix and surrounding connective tissue

• related to focal adhesions where mechanical force and regulatory signals from ECM are transmitted to cells

• made of dystrophin → prominent component of costameres

  • mutation causes severe muscle weakness and associated to muscular dystrophy

desmin

intermediate filament in muscle cells that bind to Z-lines of individual sarcomeres to serve as a link for myofilaments within myofibrils

• link sarcomeres to mitochondria, nuclear membrane, and costameres at sarcolemma