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

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A Correction to this article was published on 05 September 1996

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 cells1. Inhibitory modulation of GIRKs by G-protein-coupled receptors may have important implications in cardiac and brain physiology. Previously Gα and Gβγ subunits of heterotrimeric G proteins have both been implicated in channel opening2,3, but recent studies attribute this role primarily to the Gβγ dimer that activates GIRKs in a membrane-delimited fashion, probably by direct binding to the channel protein4–8. We report here that free GTPγS-activated Gαi1, but not Gαi2 or Gαi3, potently inhibits Gβ1γ2-induced GIRK activity in excised membrane patches of Xenopus oocytes expressing GIRK1. High-affinity but partial inhibition is produced by Gαs-GTPγS. Gαi1-GTPγS also inhibits Gβlγ2-activated GIRK in atrial myocytes. Antagonistic interactions between Gα and Gβγ may be among the mechanisms determining specificity of G protein coupling to GIRKs.

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Authors and Affiliations

  1. Institut für Medizinische Physik und Biophysik, Universitat Graz, A-8010, Graz, Austria

    Wolfgang Schreibmayer

  2. Department of Pharmacology, University of Texas, Southwestern Medical School, Dallas, Texas, 75235-9041, USA

    Carmen W. Dessauer & Alfred G. Gilman

  3. Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, 69978, Israel

    Dmitry Vorobiov & Nathan Dascal

  4. Division of Biology, California Institute of Technology, Pasadena, California, 91125, USA

    Henry A. Lester & Norman Davidson

Authors
  1. Wolfgang Schreibmayer
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  2. Carmen W. Dessauer
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  3. Dmitry Vorobiov
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  4. Alfred G. Gilman
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  5. Henry A. Lester
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  6. Norman Davidson
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  7. Nathan Dascal
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Schreibmayer, W., Dessauer, C., Vorobiov, D. et al. Inhibition of an inwardly rectifying K+ channel by G-protein α-subunits. Nature 380, 624–627 (1996). https://doi.org/10.1038/380624a0

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  • DOI: https://doi.org/10.1038/380624a0

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