Identification of a G-Protein-Independent Activator of GIRK Channels.

ABSTRACT: G-protein-gated inwardly rectifying K⁺ (GIRK) channels are essential effectors of inhibitory neurotransmission in the brain. GIRK channels have been implicated in diseases with abnormal neuronal excitability, including epilepsy and addiction. GIRK channels are tetramers composed of either the same subunit (e.g., homotetramers) or different subunits (e.g., heterotetramers). Compounds that specifically target subsets of GIRK channels in vivo are lacking. Previous studies have shown that alcohol directly activates GIRK channels through a hydrophobic pocket located in the cytoplasmic domain of the channel. Here, we report the identification and functional characterization of a GIRK1-selective activator, termed GiGA1, that targets the alcohol pocket. GiGA1 activates GIRK1/GIRK2 both

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC7401321 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature