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

Nature
W SchreibmayerN Dascal

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 alpha and G beta gamma subunits of heterotrimeric G proteins have both been implicated in channel opening, but recent studies attribute this role primarily to the G beta gamma dimer that activates GIRKs in a membrane-delimited fashion, probably by direct binding to the channel protein. We report here that free GTP gamma S-activated G alpha i 1, but not G alpha i 2 or G alpha i 3, potently inhibits G beta 1 gamma 2-induced GIRK activity in excised membrane patches of Xenopus oocytes expressing GIRK1. High-affinity but partial inhibition is produced by G alpha s-GTP gamma S. G alpha i 1-GTP gamma S also inhibits G beta 1 gamma 2-activated GIRK in atrial myocytes. Antagonistic interactions between G alpha and G beta gamma may be among the mechanisms determining specificity of G protein coupling to GIRKs.

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Citations

Oct 23, 1998·Molecular and Cellular Endocrinology·A SpadaE Ballarè
Mar 8, 2002·Cellular Signalling·Paul R Albert, Liliane Robillard
Jan 16, 1998·Cellular Signalling·N Dascal
Oct 12, 2001·Trends in Endocrinology and Metabolism : TEM·N Dascal
Apr 15, 2010·Nature Reviews. Neuroscience·Christian Lüscher, Paul A Slesinger
Jun 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Liu-Min FanSarah M Assmann
Oct 13, 2010·The Journal of Biological Chemistry·Edgar Leal-PintoDiomedes E Logothetis
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Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·C A DoupnikP Kofuji
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·M O SowellR M Mortensen
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·N MadaniD Kabat
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·D R Warner, L S Weinstein
Sep 21, 2000·European Journal of Biochemistry·M D Mark, S Herlitze
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Feb 26, 2005·The Journal of Physiology·Maki Koike-TaniYasuko Nakajima
Sep 2, 2009·The Journal of Physiology·Wolfgang Schreibmayer
Jan 28, 2003·Biophysical Journal·Carmen MüllnerWolfgang Schreibmayer
Jul 30, 2014·Frontiers in Cellular Neuroscience·Karim Nagi, Graciela Pineyro

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