Structural determinants and regulation of spontaneous activity in GABA_A receptors.

ABSTRACT: GABA_A receptors are vital for controlling neuronal excitability and can display significant levels of constitutive activity that contributes to tonic inhibition. However, the mechanisms underlying spontaneity are poorly understood. Here we demonstrate a strict requirement for β3 subunit incorporation into receptors for spontaneous gating, facilitated by α4, α6 and δ subunits. The crucial molecular determinant involves four amino acids (GKER) in the β3 subunit's extracellular domain, which interacts with adjacent receptor subunits to promote transition to activated, open channel conformations. Spontaneous activity is further regulated by β3 subunit phosphorylation and by allosteric modulators including neurosteroids and benzodiazepines. Promoting spontaneous activity reduced neur

SUBMITTER: Sexton CA 

PROVIDER: S-EPMC8443696 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature