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

The G protein-coupled inward rectifier K+ channel (GIRK) is activated by direct interaction with the heterotrimeric GTP-binding protein beta gamma subunits (G beta gamma), However, the precise role of G beta and G gamma in GIRK activation remains to be elucidated. Using transient expression of GIRK1, GIRK2, G beta 1, and G gamma 2 in human embryonic kidney 293 cells, we show that C-terminal mutants of G beta 1, which do not bind to G gamma 2, 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 G beta 1 that bind to G gamma 2, are capable of activating the GIRK channel. These results suggest that G gamma plays a more important role than that of an anchoring device for the G beta gamma-induced GIRK activation. (C) 1999 Federation of European Biochemical Societies.