Alphaxalone Binds in Inner Transmembrane β+-α- Interfaces of α1β3γ2 γ-Aminobutyric Acid Type A Receptors.

ABSTRACT: BACKGROUND:Neurosteroids like alphaxalone are potent anxiolytics, anticonvulsants, amnestics, and sedative-hypnotics, with effects linked to enhancement of γ-aminobutyric acid type A (GABAA) receptor gating in the central nervous system. Data locating neurosteroid binding sites on synaptic αβγ GABAA receptors are sparse and inconsistent. Some evidence points to outer transmembrane β-α interfacial pockets, near sites that bind the anesthetics etomidate and propofol. Other evidence suggests that steroids bind more intracellularly in β-α interfaces. METHODS:The authors created 12 single-residue β3 cysteine mutations: β3T262C and β3T266C in β3-M2; and β3M283C, β3Y284C, β3M286C, β3G287C, β3F289C, β3V290C, β3F293C, β3L297C, β3E298C, and β3F301C in β3-M3 helices. The authors coexpressed α1 and γ2

SUBMITTER: Ziemba AM 

PROVIDER: S-EPMC5771863 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature