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

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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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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