Orthosteric- versus allosteric-dependent activation of the GABA_A receptor requires numerically distinct subunit level rearrangements.

ABSTRACT: Anaesthetic molecules act on synaptic transmission via the allosteric modulation of ligand-gated chloride channels, such as hetero-oligomeric α₁β₂γ₂ GABA_A receptors. To elucidate the overall activation paradigm via allosteric versus orthosteric sites, we used highly homologous, but homo-oligomeric, ρ₁ receptors that are contrastingly insensitive to anaesthetics and respond partially to several full GABA α₁β₂γ₂ receptor agonists. Here, we coexpressed varying ratios of RNAs encoding the wild-type and the mutated ρ₁ subunits, which are anaesthetic-sensitive and respond with full efficacy to partial GABA agonists, to generate distinct ensembles of receptors containing five, four, three, two, one,

SUBMITTER: Amin J 

PROVIDER: S-EPMC5552871 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature