Referenced in: none

Automatically associated channels: Kir2.1 , Kir3.1 , Slo1

Title: Inhibition of an inwardly rectifying K+ channel by G-protein alpha-subunits.

Authors: W Schreibmayer, C W Dessauer, D Vorobiov, A G Gilman, H A Lester, N Davidson, N Dascal

Journal, date & volume: Nature, 1996 Apr 18 , 380, 624-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/8602262

Abstract
Cholinergic muscarinic, serotonergic, opioid and several other G-protein-coupled neurotransmitter receptors activate inwardly rectifying K+ channels of the GIRK family, slowing the heartbeat and decreasing the excitability of neuronal cells. Inhibitory modulation of GIRKs by G-protein-coupled receptors may have important implications in cardiac and brain physiology. Previously G alpha and G beta gamma subunits of heterotrimeric G proteins have both been implicated in channel opening, but recent studies attribute this role primarily to the G beta gamma dimer that activates GIRKs in a membrane-delimited fashion, probably by direct binding to the channel protein. We report here that free GTP gamma S-activated G alpha i 1, but not G alpha i 2 or G alpha i 3, potently inhibits G beta 1 gamma 2-induced GIRK activity in excised membrane patches of Xenopus oocytes expressing GIRK1. High-affinity but partial inhibition is produced by G alpha s-GTP gamma S. G alpha i 1-GTP gamma S also inhibits G beta 1 gamma 2-activated GIRK in atrial myocytes. Antagonistic interactions between G alpha and G beta gamma may be among the mechanisms determining specificity of G protein coupling to GIRKs.