NMJ & Muscle Contractions

• Nerve-Muscle Relationship

  Skeletal muscle must be stimulated by nerve

  
• Somatic motor neurons


  • Nerve cell bodies in brainstem/spinal cord
  • Axons reach to muscle fibers

  
• Neuromuscular junction

  Point of contact between nerve axon and muscle fiber

  
• Motor unit


  One nerve fiber (axon) + all muscle fibers innervated by it

  
• Synapse


  Where nerve fiber meets target cell

  
• Axon terminal


  • Swollen end of axon at synapse
  • Vesicles filled w/ acetylcholine (ACh) - neurotransmitter

  
• Acetylcholinesterase (AChE)


  Breaks down ACh
• Membrane potential


  Difference in electrical charge across plasma membrane

  
• Resting membrane potential

  • When muscle is at rest
  • Membrane is "polarized"
  • Intracellular space negative
  • Extracellular space positive
  • RMP = -90 mV
  • Threshold = -65mV
• Sodium-potassium pump

  Maintains resting membrane potential
• Ligand-gated channel


  Channel opened by binding of a ligand
• Voltage-gated channel

  Channel opened by changes in membrane potential

  
• Excitation


  Nerve action potentials lead to muscle action potentials
• Excitation-contraction coupling


  Action potentials on sarcolemma cause activation of myofilaments, preparing them to contract

  
• Contraction


  Muscle fiber develops tension & shortens (myosin + actin binding)

  
• Relaxation


  Stimulation ends, muscle fiber relaxes
• Excitation


  1. Nerve signal (action potential) arrives at axon terminal

  2. Stimulates opening of voltage-gated Ca2+ channels à Ca2+ enters axon terminal

  3. Calcium stimulates release of ACh

  4. Ca2+ binds to ACh vesicles à vesicles release ACh via exocytosis into synaptic cleft

  5. ACh binds to ACh receptors in sarcolemma of muscle fiber

  6. Ion channels open in ACh receptor à Na+ (lots) and K+ (some) move DOWN their concentration gradients

  7. Sodium entering cell > potassium leaving cell à sarcoplasm becomes less negative

  8. Causes local depolarization – End-plate potential (EPP)

  9. If stimulus is strong enough, membrane potential reaches threshold (-65 mV)

  10. Triggers adjacent voltage-gated ion channels to open à ACTION POTENTIAL generated

  
• Excitation-Contraction Coupling

  1. Wave of APs spreads across sarcolemma from motor end plate

  2. AP continues down into T-tubules

  3. Stimulates release of Ca2+ from terminal cistern of SR

  4. Ca2+ binds to troponin (on thin filament)

  5. Causes tropomyosin to change shape à exposes active sites where myosin can now bind

  
• Contraction

  1. Myosin head hydrolyzes ATP ( à ADP + Pi)

  2. Moves myosin head into extended/unbent position

  3. Myosin head binds to active site on actin à cross-bridge formation

  4. Myosin releases ADP & Pi à causes myosin head to snap back into its low-energy, bent position

  5. Pulls actin filament along with it

  6. Myosin then binds a new ATP à destabilizes the actin-myosin bond

  7. Myosin releases actin

  8. Myosin hydrolyzes ATP à resets à process repeated further down the filament

  
• Relaxation


  1. Nerve signal stops

  2. Release of ACh stops

  3. ACh released from receptor proteins

  4. AChE breaks down ACh (in synaptic cleft)

  5. Ca2+ release from SR stops; Ca2+ reabsorbed into SR

  6. Decrease in freely available Ca2+ à no more binding to troponin à tropomyosin blocks active sites again à no crossbridge formation