Candidate Review:

Assembly and Heterogeneity of GABAA Receptors

Katharine N. Gurba

Neuroscience Graduate Program, Vanderbilt University School of Medicine, U1205 Medical Center North, Nashville, TN 37232, USA.
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Abstract | Full Text | PDF

Abstract | GABAA receptors (GABAARs)are pentameric, ligand-gated chloride channels that mediate the majority offast inhibitory synaptic neurotransmission in the brain.  The receptors areassembled from a repertoire of 19 subunits (α1-6, β1-3, γ1-3,δ, ε, π, and ρ1-3), providing the possibility for vastisoform heterogeneity.  Because the subunit subtypes included in a receptordetermine its physiological and pharmacological properties, identification ofreceptor isoforms has clear clinical relevance.  A large body of literatureindicates that GABAARs do not assemble randomly; rather,incorporation of specific subunits into a receptor is regulated at manylevels.  Each subunit has a characteristic temporal and spatial expressionpattern; however, most neurons express many GABAAR subunits atonce.  Consequently, certain “rules” of assembly must exist to limit receptorheterogeneity.  In this review, we discuss the regulation of GABAARbiogenesis, including limitation of heterogeneity, as well as the specificreceptor isoforms that have been identified in vivo.