K1vii: Gaba Receptors

  • γ-aminobutyric acid = principle inhibitory NT of CNS; 1/3 of all CNS synapses
    • Synthesis: decarboxylation of glutamate
    • Storage: pre-synaptic nerve terminals
    • Removal
      • METABOLISM by Transamination
      • REUPTAKE into nerve terminal
  • 2 classes of GABA receptor; GABAA + GABAB

Gabaₐ

Structure

  • Pentametric
  • Inotropic (Cl–)
  • Many subunits: α, β, γ, δ, ε, ζ
  • Different GABA R have diff no. of subunits ∴30 types!
    • You need α, β, γ subunit for full function

Binding Sites

  • Different binding sites
    • Barbiturates: direct activation of Cl– channel
      • ↑duration Cl– channel opening
      • ↓dissociation of GABA
    • BZD
      • ↑frequency of GABA channel opening
    • PPF/Volatiles
      • Potentiate GABA effects
Gaba Site

Gabaь

  • Metabrotopic (GPCR)
  • ↑K+ or ↓Ca2+ channel conductance
  • Pre & post synaptic location
    • Presyn = ↑release of GABA from storage sites
    • Postsyn = generates inhibitory postsynaptic membrane potential
  • BACLOFEN = GABAB AGONIST
    • GABAB mediated inhibition of muscle contraction not affecting NMT
    • ∴↓muscle spasm in MS & SC lesions

Glycine Receptor

  • Major inhibitory NT of spinal cord & brainstem
  • Assoc with Cl– channel like GABAA
  • Volatiles markedly potentiate action of GLYCINE