PubMed 10212228

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir2.1 , Kir2.4 , Kir3.1 , Kir3.4

Title: Identification of a potassium channel site that interacts with G protein betagamma subunits to mediate agonist-induced signaling.

Authors: C He, H Zhang, T Mirshahi, D E Logothetis

Journal, date & volume: J. Biol. Chem., 1999 Apr 30 , 274, 12517-24

PubMed link:

Activation of heterotrimeric GTP-binding (G) proteins by their coupled receptors, causes dissociation of the G protein alpha and betagamma subunits. Gbetagamma subunits interact directly with G protein-gated inwardly rectifying K+ (GIRK) channels to stimulate their activity. In addition, free Gbetagamma subunits, resulting from agonist-independent dissociation of G protein subunits, can account for a major component of the basal channel activity. Using a series of chimeric constructs between GIRK4 and a Gbetagamma-insensitive K+ channel, IRK1, we have identified a critical site of interaction of GIRK with Gbetagamma. Mutation of Leu339 to Glu within this site impaired agonist-induced sensitivity and decreased binding to Gbetagamma, without removing the Gbetagamma contribution to basal currents. Mutation of the corresponding residue in GIRK1 (Leu333) resulted in a similar phenotype. Both the GIRK1 and GIRK4 subunits contributed equally to the agonist-induced sensitivity of the heteromultimeric channel. Thus, we have identified a channel site that interacts specifically with Gbetagamma subunits released through receptor stimulation.