skeletal muscle

• Muscle Characteristics


  • Excitable - respond to stimuli by producing APs
  • Contractile - can shorten, thicken
  • Extensible - stretch when pulled
  • Elastic - return to original shape after contraction or extension
• Muscle Functions


  • Movement - e.g. walking, breathing
  • Posture, facial expression
  • Heat production ⇒ 37°C
  • Protection of viscera - body wall
• Neuromuscular Junction


  • Each muscle fibre (cell) innervated by only 1 neuron
  • Axon of motor neuron branches to innervate several muscle fibres (1 neuron ⇒ ~150 fibres within same whole muscle)
  • A single motor neuron + all the muscle fibres it innervates = a motor unit
• Structure of Neuromuscular Junction


  • Presynaptic cell (neuron) with ACh (nt) in vesicles
  • Postsynaptic cell (muscle) membrane (sarcolemma) - specialized region with ACh receptors (= motor end plate)
  • Two membranes separated by synaptic cleft
• Function of Neuromuscular Junction

  1. AP reaches axon terminal and synaptic end bulb of neuron

  2. Ca2+ enters via voltage gates ⇒ causes exocytosis of ACh

  3. ACh binds to ACh receptors on motor end plate

  4. Chemical gates open and Na+ enters ⇒ End Plate Potential (EPP = a depolarizing GP)

  5. EPP causes opening of Na+ voltage gates on adjacent sarcolemma ⇒ AP (AP has same properties/channels as on a neuron) - propagates along sarcolemma
• 1 AP (neuron) → 1 EPP → 1 AP (always!)
• To inhibit skeletal muscle, must inhibit motor neuron
• Relaxed muscle


  • Tropomyosin covers myosin binding sites on the actin
  • The myosin head is activated
• Myosin Head Activation


  ATP → ADP + Pi (on myosin head) → Energy (still on myosin head) = ACTIVATED
• Muscle Contraction


  1. Excitation of muscle fibre (electrical event)

  2. Excitation-contraction coupling (electrical to mechanical event)

  3. Contraction (mechanical) = Sliding Filament Mechanism
• Steps in Excitation-Contraction Coupling

  • AP in T-tubules cause release of Ca2+ (coupling agent) from terminal cisternae of sarcoplasmic reticulum (SR) via mechanically gated channels
  • Ca2+ binds to troponin
  • Troponin-tropomyosin complex moves, exposing myosin binding sites on actin
• Sliding Filament Mechanism


  1. Activated myosin heads attach to binding sites on actin (cross bridge formation)

  2. Energy stored in myosin head is released - myosin head pivots (= POWER STROKE), ADP + Pi are released. Actin slides over myosin toward centre of sarcomere (M line)

  3. ATP attaches to myosin head, causing its release from actin + unpivot = RECOVERY STROKE

  4. Myosin head reactivates (ATP ⇒ ADP + Pi)

  5. If Ca2+ in cytosol remains high, these steps repeat
• Sarcomeres shorten, H zone and I band shorten, A band = same length, myofibrils shorten ∴ muscle shortens, thin (actin) + thick (myosin) myofilaments remain the same length
• Muscle Fibre Relaxation


  1. ACh broken down by AChE on motor end plate (facing cleft)

  2. SR actively takes up Ca2+ (Ca2+-ATPase)

  3. ATP binds to and releases myosin heads

  4. Tropomyosin moves back to cover myosin binding sites on actin when the myosin heads are released
• ATP necessary for


  • Cross bridge release (ATP not broken down)
  • Activation of myosin (ATP ⇒ ADP + Pi) + power stroke
  • Pump Ca2+ into SR
  • Fibre Na+/K+-ATPase activity
• Rigor Mortis


  "Stiffness of death" - myosin heads still activated, even after death - can bind to actin, ATP production gradually stops - no O2, intracellular Ca++ ⇑ from ECF, SR (leakage) ⇒ binding sites exposed (cross bridges form) ⇒ myosin heads not released from actin (no new ATP produced) ⇒ muscle remains contracted
• Extracellular Ca2+


  Stabilizes Na+ voltage gates (keeps them closed in absence of APs), if ECF Ca2+ low (pregnancy, lactation) → gates open spontaneously & Na+ enters fibre → depolarizes → cramps (contractions)
• Conditions/Substances causing flaccid paralysis

  • Myasthenia gravis - ⇓ in ACh receptors (autoimmune), treatment - use AChE inhibitors (⇑ binding to remaining receptors)
  • Curare Poisoning - prevents ACh from binding to receptors, was used in surgery
  • Botulism - prevents exocytosis of ACh - flaccid paralysis, medical - treat uncontrolled blinking, crossed eyes, cosmetic - Botox (wrinkles, sweating)
• Substances resulting in muscle contractions

  • Nicotine - binds to receptors + mimics ACh effect – get muscle spasms
  • Black Widow Spider Venom - massive release of ACh, could stop breathing
• Muscle Tension


  Force exerted by a muscle or muscle fibre, determined by # of cross bridges formed
• Factors affecting muscle tension in a fibre

  • Frequency of stimulation
  • Fibre length
  • Size of fibre
  • Fatigue
• Factors affecting muscle tension in a whole muscle

  • Number of fibres contracting
  • Number of fibres per motor unit
  • Muscle size
  • Fatigue
• Muscle Tone


  Low level of tension in a few fibres that develops as different groups of motor units are alternately stimulated over time, gives firmness to muscle
• Types of whole muscle contraction

  • Isotonic - muscle changes length, tension > weight of load lifted, uses ATP
  • Isometric - muscle length constant, tension less than required to move load, tension increases - cross bridges form but no shortening, uses ATP
• Energy sources for muscle contraction

  • During resting conditions: fatty acids used to produce ATP (aerobic), storage of glycogen, creatine phosphate, little ATP
  • During short term exercise (< 1 minute): use available ATP, creatine phosphate used to produce ATP, muscle glycogen ⇒ glucose ⇒ pyruvic acid ⇒ anaerobic pathway ⇒ lactic acid
  • Long term exercise (1 min to hours): ATP from aerobic pathway, glucose (from liver), fatty acids used more as exercise continues, O2 sources: blood hemoglobin + muscle myoglobin
• Causes of Muscle Fatigue

  • Physiological Fatigue: depletion of energy supplies, build-up of end products (H+, Pi), failure of APs
  • Psychological Fatigue: failure of CNS to send commands to muscles, probably due to lactic acid
• EPOC


  Excess Post-exercise O2 Consumption - recovery O2 consumption (deep rapid breathing) used to replenish stores of glycogen, C~P, O2 on Hb/myoglobin, convert lactic acid to pyruvic acid ⇒ Krebs or glucose in liver, also ⇑ in body temp from exercise = ⇑ O2 demand (faster chemical reactions)