GABA/baclofen channel

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  1. Gamma aminobutyric acid (GABA) is a major inhibitory transmitter in the brain and spinal cord
    1. glycine, a less common transmitter, is used in the spinal cord by interneurons that inhibit antagonist muscles (through Renshaw cells)
  2. GABA receptor is composed of at least 3 subunits – alpha, beta, and gamma
    1. all of the subunits bind GABA although the alpha subunit does so with the greatest affinity
    2. both alpha and beta subunits bind barbiturates but only the alpha subunit binds benzodiazepines; both benzodiazepines and barbiturates act to increase the GABA induced Cl current; the presence of GABA, benzodiazepine, or barbiturate influences the binding of the other two – e.g. a benzodiazepine will bind more tightly when GABA is bound to the receptor
    3. benzodiazepines bind more commonly in the cerebellum than the spinal cord; benzodiazepines also affect the reticular activating system in the pons
      1. benzodiazepine withdrawal may be treated with chlordiazepoxide
  3. GABA type A receptor is more common and causes a rapid increase in Cl conduction
  4. GABA type B receptor uses a G protein as a secondary messenger; baclofen is a type B agonist
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