Skeletal Nervemuscle Junction

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Skeletal Nerve-muscle Junction
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Architecture

• Nerve-muscle junction
• Each motor unit is made up of a motor neuron and
  all the muscle fibers it innervates
• Presynaptic axon boutons
• Postsynaptic muscle membrane
• Motor endplate
• Both presynaptic and postsynaptic specializations

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EM fine structure

• Presynaptic
• Large bouton, many vesicles
• Postsynaptic
• Involded muscle membrane, large surface area,
  many Ach receptors

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Nicotinic Ach receptor

• Heteromeric ionotropic channel structure
• Ach binding opens channel to small cations (Na
  K)

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The End-plate Potential

• Ligand gated depolarization
• Proportional to Ach binding
• Only occurs at the end plate
• Spreads decrementally
• Triggers V-gated channels in adjacent muscle
  membrane
• Action potentials propagate over the rest of
  muscle membrane

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Effect of Acetylcholine Esterase

• Normal action of Ach (and endplate
  depolarization) is limited by splitting into
  choline and acetate
• Antagonists to Ach-esterase result in larger and
  more prolonged endplate potential

• Acetylcholine esterase is attached
  extracellularly at the motor endplate

cholinesterase inhibitor
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mEPPs - miniature end-plate potentials

• Spontaneous release from boutons of one or a few
  vesicles
• evidence for quantal release

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Effect of Changes in Serum Calcium

• Calcium required for muscle contraction
• Involved in triggering Ach vesicle fusion
  (pre-synaptic) and contractile filaments
  (post-synaptic)
• Normal changes in serum calcium dont affect Ach
  release (large safety factor)
• Changes do affect muscle excitability

• Hypercalcemia-higher than normal calcium
• Muscle membrane is less excitable-muscle weakness
• Hypocalcemia-lower than normal calcium
• Muscle membrane is more excitable-random/spontaneo
  us muscle twitching

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NMJ versus CNS Synapses

• Similarities
• NT synthesized presynaptically
• Stored in vesicle
• Calcium-dependent exocytosis
• Activates post-synaptic receptor to cause change
  in ion permeability/membrane potential
• Neurotransmitter action terminated by specific
  mechanisms

• Differences
• NMJ Only
• 1 type of pre-synaptic axon
• 1 neurotransmitter (Ach)
• Ach is only excitatory
• Each AP releases lots of Ach
• Each EPP is above threshold for AP
• CNS Only
• Many types of pre-synaptic axons
• Many NT types converge on single neuron
• Mix of excitatory/inhibitory/modulatory
• Each PSP is small summation required for AP

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Some sites for disorders of the motor unit