Inhibition of an inwardly rectifying K+ channel by G-protein α-subunits

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

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


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(α) and G(βγ) Subunits of heterotrimeric G proteins have both been implicated in channel opening, but recent studies attribute this role primarily to the G(βγ) dimer that activates GIRKs in a membrane-delimited fashion, probably by direct binding to the channel protein. We report here that free GTPγS-activated G(αi1), but not G(αi2) or G(αi3), potently inhibits G(β1γ2)-induced GIRK activity in excised membrane patches of Xenopus oocytes expressing GIRK1. High-affinity but partial inhibition is produced by G(αs)-GTPγS. G(αi1)-GTPγS also inhibits G(β1γ2)-activated GIRK in atrial myocytes. Antagonistic interactions between G(α) and G(βγ) may be among the mechanisms determining specificity of G protein coupling to GIRKs.

Original languageEnglish (US)
Pages (from-to)624-627
Number of pages4
Issue number6575
StatePublished - Apr 18 1996

ASJC Scopus subject areas

  • General


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