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

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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(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
JournalNature
Volume380
Issue number6575
DOIs
StatePublished - 1996

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    Schreibmayer, W., Dessauer, C. W., Vorobiov, D., Gilman, A. G., Lester, H. A., Davidson, N., & Dascal, N. (1996). Inhibition of an inwardly rectifying K+ channel by G-protein α-subunits. Nature, 380(6575), 624-627. https://doi.org/10.1038/380624a0