Updated: 11/3/2021

Action Potential Conduction

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  • A 36-year-old male presents with ascending muscle weakness. The patient is generally healthy, with no pertinent past medical history. He states he recently recovered from diarrhea that has lasted over a week. Neurological examination is notable for weakness in the lower extremities and an abscence of patellar reflexes. (Botulinum toxin)
  • Action Potential Overview  
    • initiation
      • neuronal membrane potential becomes more positive → opening of voltage gated Na+ channels
        • positive feedback loop
        • threshold is reached → action potential generated
    • propagation
      • action potential generated at one portion of neuron → excitation of adjacent neuronal membrane
        • signal thus propagates down the axon via opening of voltage gated Na+ channels
    • neuromuscular junction
      • when the propagated action potential reaches the presynaptic neuron, it becomes depolarized
        • this opens voltage gated Ca2+ channels
          • allows release of acetylcholine (ACh) from stored vesicles in the presynaptic neuron
      • released ACh act on nicotinic receptors (a ligand-gated ion channel) on the motor end plate
        • motor end plate depolarizes, and propagates the action potential down the muscle fiber, ultimately leading to muscle contraction
Action Potential Initiation
  • Initiation
    • initial depolarization → opening of voltage gated Na+ channels
      • increased Na+ inflow → opening of more voltage gated Na+ channels (positive feedback loop)
        • threshold is eventually met → action potential generation
      • clinical correlate
        • tetrodotoxin (pufferfish consumption) binds fast voltage-gated Na+ channels in nerve tissue, which does not allow for depolarization or action potential formation
          • can result in nausea, weakness, dizziness or can be fatal
          • treatment is supportive
 Action Potential Propagation
  • Propagation
    • depolarized region of the neuronal membrane → excitation of adjacent neuronal membrane
    • myelinated neurons
      • Schwann cells myelinates axons of the peripheral nervous system (PNS)
        • myelinates only 1 axon
        • increases conduction velocity 
        • non-myelinated areas are called Nodes of Ranvier
          • contains a high concentration of Na+ channels
            • allows "jumping" of action potential from one Node of Ranvier to the next
              • this is saltatory conduction
        • clinical correlate
          • Guillain-Barre syndrome
            • autoimmune destruction of peripheral myelinated neurons
              • classically associated with previous Campylobacter jejuni infection
      • myelinated neuron examples
        • sensory
          • Pacinian corpuscles transmit vibrational sense and pressure via large, myelinated fibers 
    • non-myelinated neurons
      • transmit potentials via Na+ channels that exist along the entire length of the axon (no Nodes of Ranvier)
        • have same refractory period of Na+ channels as myelinated axons do but at a slower velocity of conduction due to lack of insulation (myelin)
Neuromuscular Junction

  • Neuromuscular junction 
    • propagated action potential reaches presynaptic neuron opens voltage gated Ca2+ channels
      • clinical correlate
        • Lambert-Eaton syndrome
          • autoantibodies against the presynaptic calcium channels → reduced ACh release → weakness
          • associated with small cell carcinoma of the lung
    • Ca2+ influx → ACh release with the help of SNARE proteins
      • clinical correlate
        • botulinum toxin
          • cleaves SNARE proteins → decreased ACh release → flaccid paralysis
        • tetanus toxin
          • cleaves SNARE proteins → decrease release of inhibitory neurotransmitters (GABA and glycine) in the spinal cord → spasticity and overactivity
    • released ACh act on nicotinic receptors (ligand gated ion channels) of the motor end plate
      • clinical correlate
        • myasthenia gravis
          • autoantibodies bind the post-synaptic ACh receptor → weakness
    • depolarization travels along the muscle cell via T-tubules, which are invaginations that allow for the skeletal muscle to be depolarized
    • dihydropyridine receptors are then depolarized
      • mechanically coupled to ryanodine receptors (Ca2+ release channels) on the sarcoplasmic reticulum
        • increases intracellular Ca2+ concentration → binds to troponin C → cross bridge cycle
          • See Skeletal and Cardiac Muscle Contractions topic
        • clinical correlate
          • malignant hyperthermia
            • ryanodine or dihydropyridine receptor mutation → unregulated Ca2+ release into the muscle cytoplasm → sustained muscle contraction → increased aerobic metabolism → depletion of O2, ATP, and increased CO2 production and acidosis
            • treatment: dantrolene

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