Analysis of GABA Receptor Assembly and Function in Targeted Mutant Mice

摘要: GABA is the major inhibitory neurotransmitter in central nervous system, acting via ionotropic GABAA receptors and metabotropic GABAB receptors. are molecular substrates for regulation of vigilance, anxiety, muscle tension, epileptogenic activity memory functions enhancement receptor-mediated fast synaptic inhibition basis pharmacotherapy various neurological psychiatric disorders. The receptor a target treatment spasticity, migraine headache musculoskeletal pain. pentameric complexes assembled from repertoire at least 18 subunits (α1-oα6, β1-β3,γ1-γδ∈,o,ρ1-σ3), whereas heterodimers composed GABAB1 GABAB2 subunits. Two kinds receptor-targeted mutant mice have been generated: (1) knock-out which lack individual (α1, α5, α6, β2, β3, γ2, δ, ρ1) (2) knock-in carry point mutations affecting action modulatory drugs [α1(H101R), α2(H101R), α3(H126R) α5(H105R)]. With regard to receptor, subunit has knocked out. Whereas knockout provided information primarily with respect gene transcription, assembly some physiological subtypes, point-mutated mice, specific subtypes insensitive diazepam, revealed contribution broad pharmacological spectrum diazepam. insights obtained studying targeting expected aid development novel subtype-specific fewer side effects than currently clinical use.