Membrane cholesterol dependence of cannabinoid modulation of glycine receptor.

ABSTRACT: Cannabinoids exert therapeutic effects on several diseases such as chronic pain and startle disease by targeting glycine receptors (GlyRs). Our previous studies have shown that cannabinoids target a serine residue at position 296 in the third transmembrane helix of the α1/α3 GlyR. This site is located on the outside of the ion channel protein at the lipid interface where the cholesterol concentrates. However, whether membrane cholesterol regulates cannabinoid-GlyR interaction remains unknown. Here, we show that GlyRs are closely associated with cholesterol/caveolin-rich domains at subcellular levels. Membrane cholesterol reduction significantly inhibits cannabinoid potentiation of glycine-activated currents in cultured spinal neurons and in HEK 293T cells expressing α1/α3 GlyRs. Such inhib

SUBMITTER: Yao L 

PROVIDER: S-EPMC8147113 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature