Importance of the G protein γ subunit in activating G protein‐coupled inward rectifier K+ channels

Abstract
The G protein‐coupled inward rectifier K+ channel (GIRK) is activated by direct interaction with the heterotrimeric GTP‐binding protein βγ subunits (Gβγ). However, the precise role of Gβ and Gγ in GIRK activation remains to be elucidated. Using transient expression of GIRK1, GIRK2, Gβ1, and Gγ2 in human embryonic kidney 293 cells, we show that C‐terminal mutants of Gβ1, which do not bind to Gγ2, are still able to associate with GIRK, but these mutants are unable to induce activation of GIRK channels. In contrast, other C‐terminal mutants of Gβ1 that bind to Gγ2, are capable of activating the GIRK channel. These results suggest that Gγ plays a more important role than that of an anchoring device for the Gβγ‐induced GIRK activation.