Mutual action by Gγ and Gβ for optimal activation of GIRK channels in a channel subunit-specific manner.

ABSTRACT: The tetrameric G protein-gated K⁺ channels (GIRKs) mediate inhibitory effects of neurotransmitters that activate G_i/o-coupled receptors. GIRKs are activated by binding of the Gβγ dimer, via contacts with Gβ. Gγ underlies membrane targeting of Gβγ, but has not been implicated in channel gating. We observed that, in Xenopus oocytes, expression of Gγ alone activated homotetrameric GIRK1* and heterotetrameric GIRK1/3 channels, without affecting the surface expression of GIRK or Gβ. Gγ and Gβ acted interdependently: the effect of Gγ required the presence of ambient Gβ and was enhanced by low doses of coexpressed Gβ, whereas excess of either Gβ or Gγ imparted suboptimal activation, possibly by sequestering the other subunit "away" from the channel. The unique distal C-termi

SUBMITTER: Tabak G 

PROVIDER: S-EPMC6346094 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature