GABA and astrocytic cholesterol determine the lipid environment of GABA_AR in cultured cortical neurons.

ABSTRACT: The γ-aminobutyric acid (GABA) type A receptor (GABA_AR), a GABA activated pentameric chloride channel, mediates fast inhibitory neurotransmission in the brain. The lipid environment is critical for GABA_AR function. How lipids regulate the channel in the cell membrane is not fully understood. Here we employed super resolution imaging of lipids to demonstrate that the agonist GABA induces a rapid and reversible membrane translocation of GABA_AR to phosphatidylinositol 4,5-bisphosphate (PIP₂) clusters in mouse primary cortical neurons. This translocation relies on nanoscopic separation of PIP₂ clusters and lipid rafts (cholesterol-dependent ganglioside clusters). In a resting state, the GABA_AR associates with lipid rafts and thi

SUBMITTER: Yuan Z 

PROVIDER: S-EPMC11092523 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature