Home NEUR 310 Tuesday, March 11, 2014

Tuesday, March 11, 2014 CC-BY-NC
Sodium channels

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1Sodium channels subtypes

  • many different types for different tissues
  • brain: Na_v1.1 , 1.2, 1.6
  • diseases related to mutations: epilepsy and pain syndrome

2SMEI

  • severe myoclonic epilepsy of infancy
  • infants die before surviving to adulthood, so this is a mutation, not inherent disease
  • mutation at Nav1.1, which is encoded by SCN1A gene
  • SCN1A KO mice has severe epilepsy
  • reason
    • this sodium channel is mostly expressed in inhibitory neurons
    • inhibitory neurons cannot function -> less inhibition -> more excitation -> epilepsy
    • evidence: sodiun current in KO is affected in inhibitory neurons (bipolar cells) but not excitatory neurons (pyramidal cells)

2.1Pain Syndrome

  • Nav1.7 and 1.8 are present on pain neurons
  • 1.7 is TTX sensitive and 1.8 TTX resistant
  • 1.7 is activated first, and then it drives more depolarization and then 1.8 opens
  • 1.8 seems to be expressed exclusively in pain neurons, so lots of research is being done to try to target it.
    • this channel is also the major contributor to the action potential upstroke in small DRG neurons

2.2Inherited Erythromyelalgia (IE)

  • autosomal dominant
  • episodes of redness and pains in feet and hands
  • caused by mutation in Nav1.7
    • this mutation makes the sodium channel open easier

2.3PEPD

  • autosomal dominant
  • paroxysmal extreme pain disorder
  • pain in rectal, ocular and submndibular
  • also mutation in 1.7, in this case channels are not competely inactivated, causing persistent sodium currents

2.4Congenital inability to experience pain

  • mutation at Nav1.7, loss of function
  • recessive