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

Schreibmayer, Wolfgang and Dessauer, Carmen W. and Voroblov, Dmitry and Gilman, Alfred G. and Lester, Henry A. and Davidson, Norman and Dascal, Nathan (1996) Inhibition of an inwardly rectifying K^+ channel by G-protein ɑ-subunits. Nature, 380 (6575). pp. 624-627. ISSN 0028-0836. doi:10.1038/380624a0.

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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_(αil), 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_(αil)-GTPγS also inhibits G_(βlγ2)-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.

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Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1996 Nature Publishing Group. Received 18 October 1995; accepted 5 February 1996. We thank E. Peralta and J. P. Adelman for the cDNAs of m2 receptor and rcKATP (Kir3.4), respectively, B. Posner for providing G1i;-c685, and M. Malca for oocyte injections. Antisense ODNs to Xenopus G proteins were prepared by W. S. Marshall and co-workers of Amgen Boulder Inc. This work was supported by the Human Frontiers Scientific Program, Israel-USA Binational Science Foundation, Austrian National Bank, Spezialforschungbereich: Biomembranes and Atherosklerosis (Austria), National Institutes of Health, National Institute of General Medical Sciences, and the National Institute of Mental Health.
Funding AgencyGrant Number
Human Frontier Science ProgramUNSPECIFIED
Binational Science Foundation (USA-Israel)UNSPECIFIED
Austrian National BankUNSPECIFIED
Spezialforschungbereich Biomembranes and Atherosklerosis (Austria)UNSPECIFIED
National Institute of General Medical SciencesUNSPECIFIED
National Institute of Mental Health (NIMH)UNSPECIFIED
Issue or Number:6575
Record Number:CaltechAUTHORS:20150610-111824247
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Official Citation:Inhibition of an inwardly rectifying K+ channel by G-protein α-subunits 624-627 Wolfgang Schreibmayer, Carmen W. Dessauer, Dmitry Vorobiov, Alfred G. Gilman, Henry A. Lester, Norman Davidson & Nathan Dascal doi:10.1038/380624a0
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58161
Deposited By: Ruth Sustaita
Deposited On:10 Jun 2015 18:37
Last Modified:10 Nov 2021 22:00

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