title: Inhibition of an inwardly rectifying K+ channel by G-protein alpha-subunits.
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.
authors.affiliation: Institut für Medizinische Physik und Biophysik, Universitat Graz, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Schreibmayer
authors.forename: C W
authors.initials: CW
authors.lastname: Dessauer
authors.forename: D
authors.initials: D
authors.lastname: Vorobiov
authors.forename: A G
authors.initials: AG
authors.lastname: Gilman
authors.forename: H A
authors.initials: HA
authors.lastname: Lester
authors.forename: N
authors.initials: N
authors.lastname: Davidson
authors.forename: N
authors.initials: N
authors.lastname: Dascal
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009865:Oocytes; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014981:Xenopus
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D016376:Oligonucleotides, Antisense; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011994:Recombinant Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins