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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. http://resolver.caltech.edu/CaltechAUTHORS:20150610-111824247

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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_(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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/380624a0DOIArticle
http://www.nature.com/nature/journal/v380/n6575/abs/380624a0.htmlPublisherArticle
http://rdcu.be/yb8UPublisherFree ReadCube access
ORCID:
AuthorORCID
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.
Funders:
Funding AgencyGrant Number
Human Frontier Science ProgramUNSPECIFIED
Binational Science Foundation (USA-Israel)UNSPECIFIED
Austrian National BankUNSPECIFIED
Spezialforschungbereich Biomembranes and Atherosklerosis (Austria)UNSPECIFIED
NIHUNSPECIFIED
National Institute of General Medical SciencesUNSPECIFIED
National Institute of Mental Health (NIMH)UNSPECIFIED
Record Number:CaltechAUTHORS:20150610-111824247
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20150610-111824247
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
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:10 Jun 2015 18:37
Last Modified:08 Nov 2017 00:18

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