topic 5

• Skeletal Muscles

  • Striated
  • Multinucleated
  • Voluntary control
  • Associated with the limbs & skeleton
  • Transverse (T) tubule
  • No intercalating disk
• Structure of skeletal muscles plays a vital role in how they 'contract' to produce force - varies for all types of muscle
• The nervous system causes ONLY excitation, to stop a muscle contraction you must control the excitatory neuron
• Speed of contraction

  Slow-fast; greatest variety and fastest muscle
• Rapid contraction


  • Used for writing, talking, articulation, etc
• Slow contraction

  • Postural muscles that keep us upright
• Organisation of skeletal muscles

  1. Bundles of muscle fascicles, each covered by a connective tissue sheath called the perimysium

  2. The whole tissue is covered by epimysium (connective tissue)

  3. A fascicle is a bundle of muscle fibres (cells) + blood cells + extracellular fluid + nerves
• Fascicle organisation and separation


  • Allows the nervous system to trigger a specific amount of force by not activating all fascicles
  • Grading of force used = grading number of muscle cells used
• Myocyte (muscle fibre cell)


  Defined by a sarcolemma (plasma membrane), surrounded by endomysium (connective tissue)
• Structure of myocytes

  1. Consist of myofibril proteins --> repeating sarcomeres of myofilaments (thin & thick filaments) and other molecules

  2. Parallel myofibrils with overlapping thin/thick elements create the stripy pattern

  3. Repeating units of sarcomeres - run from Z line/disk to Z-line/disk
• Sarcomere


  The functional unit of the myocytes, consist of thick myosin II filaments and thin actin filaments
• Sarcomere structure

  • 1 thick filament : 9 thin filaments (thin filaments surround the thick filament)
  • Includes other proteins like Titin & Nebulin
  • 1 Z-line/disk next to one another, alpha-actin homodimers as antiparallel disks and many other proteins serve as anchorage points
  • I band --> only thin filament, lighter in colour; A band --> thick filaments + some overlap, darker
• Components of the Sarcomere


  • Contractile proteins
  • Regulatory proteins
  • Structural proteins
• Contractile Proteins

  Proteins that interact that cause muscles to produce force - myosin & actin
• Myosin filament


  • Large (MW 470,000 Daltons), 2 heavy chains & 4 light chains (2 light chains each)
  • Heavy chains consist of a head, a flexible hinge region to allow for head movement, and a long rigid tail - two heavy chains intertwined in an alpha-helical supercoil (insoluble, rod-like, stable)
  • Light chains are wrapped around the heavy chains - essential and regulatory
• Essential light chains


  Controls ATPase activity, plays a role in interaction between myosin and actin
• Regulatory light chains


  Phosphorylated, impacts the way myosin and actin interact
• Myosin head

  • Has two binding sites to hydrolyse ATP and interact with actin
• Actin filament (F-actin)


  • Formed from beads of G-actin molecules, using ATP
  • Each G-actin molecule has a binding site for a myosin globular head
  • Troponin & Tropomyosin (TN-TM complex) as regulatory proteins
  • Has a (-) end (free) and a (+) end - G-actin polymerisation occurs faster at + end (Z-disk end)
  • Ends of the filaments are capped for stability by tropomodulin (- end) and CapZ (+ end, also contains alpha-actinin)
• Regulatory Proteins

  Tropomyosin (TM) and Troponin (TN) complex
• Regulation of actin-myosin binding

  1. Small TM filament lies across myosin-binding sites on actin, by moving the troponin complex (made of TnT, TnC, & TnI), we can expose the binding site

  2. Movement of troponin away from binding site is caused by a conformation change, in turn caused by Ca2+ binding to TnC, now myosin may bind to actin
• Structural Proteins

  • Titin (connectin)
  • Nebulin
• Titin (connectin)

  • Longest protein in the world, > 1um in length
  • Molecular spring (elastic band) - anchors myosin to Z-disk on both ends, allows myosin to contract and pull itself towards the middle
  • Passive tension - limits range of motion of sarcomere and thus influences the passive elasticity of muscles
• Nebulin

  • Very large actin binding protein (~650 kDa), binds up to 200 actin monomers
  • Runs full length of thin filament from Z-disk + end to tropomodulin-capped - end
  • Gives the actin structure and allows for lengthening during development
• Sarcoplasmic Reticulum (SR)


  • Specialised smooth endoplasmic reticulum (sER) of muscles
  • Stores, releases, and retrieves Ca2+ (after a brief release for muscle contraction, for re-storage)
• Triggering a muscle contraction

  1. Muscle AP is at the endplate (surface), which triggers release of Ca2+ from SR stores (deep)

  2. Diameter of muscle fibres is up to 100um (pretty wide)

  3. Solution: deep periodic invaginations called T-tubules (transverse) from the sarcolemma into the sarcoplasm

  4. To maximise the chance of current flow into the T-tubules, they're flanked on both sides by enlargements of the SR called terminal cisternae

  5. Triad --> Each T-tubule and the two cisternae on either side (sandwiched tubule between 2 SR), surround myofibrils of actin & myosin
• Cross-bridge Cycling


  1. Ca2+ binds to troponin (TnC), causes a conformation change which pulls tropomyosin away from the binding site

  2. ATP binds to myosin, releasing it from the actin (head is in low energy configuration, bent)

  3. ATP gets broken down to ADP + Pi, which causes the myosin head to fall forwards, after which it springs back to high energy configuration, upright

  4. As it does so, it hits the actin binding site, ADP + Pi is released which strengthens the attachment

  5. Myosin twists a bit to ensure its facing the binding site on the next-adjacent actin filament, this continues in a spiral as cross bridges are formed and contract

  6. Myosin head bends down towards the M-line, pulling actin along, allowing the filaments to move ~10nm inwards --> power stroke

  7. Z lines move inwards, sarcomere contracts and becomes shorter
• Sliding Filament Model of Muscle Contraction

  • Z-lines move closer together, I band becomes smaller, A band stays the same width, filaments slide past one another
  • In this way, the muscle can develop tension (to hold a load) or change muscle length (to move a load)
  • At full contraction, thick and thin filaments overlap completely
• ATP works to detach the myosin from the actin, if ATP isnt available (in death), muscles remain contracted, causing Rigor Mortis ~4 hours past death
• Asynchronous cross bridges and power strokes


  • Occurs in a graded pattern, as some bridges form others detach and vice versa, allowing for a smooth motion
  • Sarcomere keeps a constant tension across time, without falls between each cycle
• Passive tension


  Observed when resting muscle is stretched, reflects the passive elastic property of muscles, caused by the connective tissue and titin/nebulin filaments, not associated with contraction
• Active tension


  Force is generated by cross bridges during contraction, relates to the degree of overlap of thick and thin filaments
• Optimal muscle length

  • Optimal length - overlap allows all cross-bridges to attach and generate maximum force, at REST
  • Longer (Stretched) length - less overlap, reduces force
  • Shorter (Compressed) length - double overlap of thin filaments, Z-lines hit ends of thick filaments which causes them to buckle, less Ca2+ is released
• The total length is a combination of active and passive tension, passive increases with muscle stretch while active decreases
• Activating Muscle to produce Force


  1. Alpha motor neurons make contact with skeletal muscle fibres at NMJ on motor end plates

  2. NMJ transmitter is ACh which binds to a nicotinic ACh receptor (nAChR)

  3. Binds two ACh to alpha subunit on ion channel to open it

  4. Influx of Na+ and Ca2+ (and efflux of K+) causes depolarisation called End Plate Potential (EPP)

  5. Triggers postsynaptic muscle AP

  6. Size of EPP = amount of ACh that binds to AChR
• Coupling Excitation to Contraction at skeletal muscle

  1. AP travels down T-tubule

  2. Encounters dihydropyridine (DHP) voltage sensors that are physically lined to ryanodine receptors (RyR)

  3. Conformational change in DHP sensor causes mechanically-gated RyR channels to open

  4. Ca2+ flows out from the SR to the sarcoplasm

  5. Ca2+ binds to troponin, which moves tropomyosin, and muscle can contract

  6. Ca2+ is pumped back into SR and tropomyosin shields actin binding site again
• Muscle 'twitch' contraction


  • Quick muscle twitch action potential, followed by a latent period between start of contraction
  • Twitch muscle AP is longer than nerve AP by the order of 10ms in skeletal muscle, and even longer in cardiac muscle
  • Slow contraction followed by slower relaxation
• Muscle Metabolism


  • Resting muscle ATP
  • Aerobic metabolism (fatty acids)
  • Anaerobic glycolysis
• Resting muscle ATP

  • At rest muscles break down fatty acids to create ATP and glucose --> glycogen (storage)
  • Excess ATP is used to turn creatine --> creatine phosphate (CP) (storage)
  • Using the enzyme creatine phosphokinase (CPK), ADP --> ATP
• Aerobic metabolism (fatty acids)


  • Primary energy source in resting muscle and moderate exercise (95% of ATP)
  • Fatty acids, carbohydrates, and proteins are broken down --> 2 ATP /pyruvate, 34 ATP / glucose = 36 ATP
  • Requires constant O2 for citric acid cycle, can use O2 stored in myoglobin