Collision coupling in the GABAB receptor–G protein–GIRK signaling cascade

Abstract

The signaling cascade comprising the 4-aminobutyrate(B) receptor (GABABR), G protein and the G protein-gated K+ channel (GIRK) mediates neuronal inhibition in the brain. Precoupling between components of the pathway (within a permanent macromolecular complex) has been proposed, but this remains debatable. We investigated this mechanism in Xenopus oocytes by varying the expression of the GABABR. Increased expression of GABABR accelerates activation of GIRK by agonist, implying that some of the components in this cascade interact by a classical collision mechanism. We also find that GABABR has a bidirectional effect on the basal activity of the GIRK channel. Our results suggest a complex mechanism of coupling between GABABR and GIRK which involves elements of both precoupling and collision coupling.