Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Physiol
2007 May 15;581Pt 1:17-32. doi: 10.1113/jphysiol.2006.125864.
Show Gene links
Show Anatomy links
Galphai3 primes the G protein-activated K+ channels for activation by coexpressed Gbetagamma in intact Xenopus oocytes.
Rubinstein M, Peleg S, Berlin S, Brass D, Dascal N.
???displayArticle.abstract???
G protein-activated K+ channels (GIRK) mediate postsynaptic inhibitory effects of neurotransmitters in the atrium and in the brain by coupling to G protein-coupled receptors (GPCRs). In neurotransmitter-dependent GIRK signalling, Gbetagamma is released from the heterotrimeric Galphabetagamma complex upon GPCR activation, activating the channel and attenuating its rectification. Now it becomes clear that Galpha is more than a mere Gbetagamma donor. We have proposed that Galphai3-GDP regulates GIRK gating, keeping its basal activity low but priming (predisposing) the channel for activation by agonist in intact cells, and by Gbetagamma in excised patches. Here we have further investigated GIRK priming by Galphai3 using a model in which the channel was activated by coexpression of Gbetagamma, and the currents were measured in intact Xenopus oocytes using the two-electrode voltage clamp technique. This method enables the bypass of GPCR activation during examination of the regulation of the channel in intact cells. Using this method, we further characterize the priming phenomenon. We tested and excluded the possibility that our estimates of priming are affected by artifacts caused by series resistance or large K+ fluxes. We demonstrate that both Galphai3 and membrane-attached Gbetagamma scavenger protein, m-phosducin, reduce the basal channel activity. However, Galphai3 allows robust channel activation by coexpressed Gbetagamma, in sharp contrast to m-phosducin, which causes a substantial reduction in the total Gbetagamma-induced current. Furthermore, Galphai3 also does not impair the Gbetagamma-dependent attenuation of the channel rectification, in contrast to m-phosducin, which prevents this Gbetagamma-induced modulation. The Galphai3-induced enhancement of direct activation of GIRK by Gbetagamma, demonstrated here for the first time in intact cells, strongly supports the hypothesis that Galphai regulates GIRK gating under physiological conditions.
Baumgartner,
Two-microelectrode voltage clamp of Xenopus oocytes: voltage errors and compensation for local current flow.
1999, Pubmed,
Xenbase
Baumgartner,
Two-microelectrode voltage clamp of Xenopus oocytes: voltage errors and compensation for local current flow.
1999,
Pubmed
,
Xenbase Bender,
Acute desensitization of GIRK current in rat atrial myocytes is related to K+ current flow.
2004,
Pubmed Bettahi,
Contribution of the Kir3.1 subunit to the muscarinic-gated atrial potassium channel IKACh.
2002,
Pubmed Bichet,
The I-II loop of the Ca2+ channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit.
2000,
Pubmed
,
Xenbase Chen,
Constitutively active G-protein-gated inwardly rectifying K+ channels in dendrites of hippocampal CA1 pyramidal neurons.
2005,
Pubmed Clancy,
Pertussis-toxin-sensitive Galpha subunits selectively bind to C-terminal domain of neuronal GIRK channels: evidence for a heterotrimeric G-protein-channel complex.
2005,
Pubmed
,
Xenbase Dascal,
Signalling via the G protein-activated K+ channels.
1997,
Pubmed Dascal,
Voltage clamp recordings from Xenopus oocytes.
2001,
Pubmed
,
Xenbase Doupnik,
Intrinsic gating properties of a cloned G protein-activated inward rectifier K+ channel.
1995,
Pubmed
,
Xenbase Fakler,
Strong voltage-dependent inward rectification of inward rectifier K+ channels is caused by intracellular spermine.
1995,
Pubmed
,
Xenbase Finley,
betaL-betaM loop in the C-terminal domain of G protein-activated inwardly rectifying K(+) channels is important for G(betagamma) subunit activation.
2004,
Pubmed
,
Xenbase Hommers,
Regulation of the inward rectifying properties of G-protein-activated inwardly rectifying K+ (GIRK) channels by Gbeta gamma subunits.
2003,
Pubmed Huang,
Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation.
1995,
Pubmed
,
Xenbase Huang,
Binding of the G protein betagamma subunit to multiple regions of G protein-gated inward-rectifying K+ channels.
1997,
Pubmed Ito,
Background conductance attributable to spontaneous opening of muscarinic K+ channels in rabbit sino-atrial node cells.
1994,
Pubmed Ivanina,
Galphai1 and Galphai3 differentially interact with, and regulate, the G protein-activated K+ channel.
2004,
Pubmed
,
Xenbase Ivanina,
Mapping the Gbetagamma-binding sites in GIRK1 and GIRK2 subunits of the G protein-activated K+ channel.
2003,
Pubmed
,
Xenbase Jiang,
The barium site in a potassium channel by x-ray crystallography.
2000,
Pubmed Kitamura,
Tertiapin potently and selectively blocks muscarinic K(+) channels in rabbit cardiac myocytes.
2000,
Pubmed Kowdley,
Hyperpolarization-activated chloride currents in Xenopus oocytes.
1994,
Pubmed
,
Xenbase Kunkel,
Identification of domains conferring G protein regulation on inward rectifier potassium channels.
1995,
Pubmed
,
Xenbase Lavine,
G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase.
2002,
Pubmed
,
Xenbase Leaney,
The G protein alpha subunit has a key role in determining the specificity of coupling to, but not the activation of, G protein-gated inwardly rectifying K(+) channels.
2000,
Pubmed Lim,
A G protein-gated K channel is activated via beta 2-adrenergic receptors and G beta gamma subunits in Xenopus oocytes.
1995,
Pubmed
,
Xenbase Logothetis,
The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart.
,
Pubmed Lopatin,
The mechanism of inward rectification of potassium channels: "long-pore plugging" by cytoplasmic polyamines.
1995,
Pubmed
,
Xenbase Lu,
Mechanism of rectification in inward-rectifier K+ channels.
2004,
Pubmed Lüscher,
G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons.
1997,
Pubmed Makary,
Base of pore loop is important for rectification, activation, permeation, and block of Kir3.1/Kir3.4.
2006,
Pubmed
,
Xenbase Matsuda,
Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+.
,
Pubmed Nagel,
CFTR fails to inhibit the epithelial sodium channel ENaC expressed in Xenopus laevis oocytes.
2005,
Pubmed
,
Xenbase Nishida,
Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution.
2002,
Pubmed Pegan,
Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification.
2005,
Pubmed
,
Xenbase Peleg,
G(alpha)(i) controls the gating of the G protein-activated K(+) channel, GIRK.
2002,
Pubmed
,
Xenbase Petit-Jacques,
Synergistic activation of G protein-gated inwardly rectifying potassium channels by the betagamma subunits of G proteins and Na(+) and Mg(2+) ions.
1999,
Pubmed
,
Xenbase Rebois,
Heterotrimeric G proteins form stable complexes with adenylyl cyclase and Kir3.1 channels in living cells.
2006,
Pubmed
,
Xenbase Reuveny,
Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits.
1994,
Pubmed
,
Xenbase Rishal,
Gbetagamma-dependent and Gbetagamma-independent basal activity of G protein-activated K+ channels.
2005,
Pubmed
,
Xenbase Rishal,
Na+ promotes the dissociation between Galpha GDP and Gbeta gamma, activating G protein-gated K+ channels.
2003,
Pubmed
,
Xenbase Riven,
GIRK channel activation involves a local rearrangement of a preformed G protein channel complex.
2006,
Pubmed Sakmann,
Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart.
,
Pubmed Schreibmayer,
Voltage clamping of Xenopus laevis oocytes utilizing agarose-cushion electrodes.
1994,
Pubmed
,
Xenbase Sharon,
Positive and negative coupling of the metabotropic glutamate receptors to a G protein-activated K+ channel, GIRK, in Xenopus oocytes.
1997,
Pubmed
,
Xenbase Shyng,
Depletion of intracellular polyamines relieves inward rectification of potassium channels.
1996,
Pubmed
,
Xenbase Signorini,
Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2.
1997,
Pubmed Slesinger,
Identification of structural elements involved in G protein gating of the GIRK1 potassium channel.
1995,
Pubmed
,
Xenbase Smirnov,
Alteration of the transmembrane K+ gradient during development of delayed rectifier in isolated rat pulmonary arterial cells.
1994,
Pubmed Stanfield,
Constitutively active and G-protein coupled inward rectifier K+ channels: Kir2.0 and Kir3.0.
2002,
Pubmed Torrecilla,
G-protein-gated potassium channels containing Kir3.2 and Kir3.3 subunits mediate the acute inhibitory effects of opioids on locus ceruleus neurons.
2002,
Pubmed Vandenberg,
Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions.
1987,
Pubmed Vivaudou,
Probing the G-protein regulation of GIRK1 and GIRK4, the two subunits of the KACh channel, using functional homomeric mutants.
1997,
Pubmed
,
Xenbase Wellner-Kienitz,
Voltage dependence of ATP-dependent K+ current in rat cardiac myocytes is affected by IK1 and IK(ACh).
2004,
Pubmed Wiser,
Modulation of basal and receptor-induced GIRK potassium channel activity and neuronal excitability by the mammalian PINS homolog LGN.
2006,
Pubmed
,
Xenbase Yakubovich,
Kinetic modeling of Na(+)-induced, Gbetagamma-dependent activation of G protein-gated K(+) channels.
2005,
Pubmed
,
Xenbase Yamada,
Spermine gates inward-rectifying muscarinic but not ATP-sensitive K+ channels in rabbit atrial myocytes. Intracellular substance-mediated mechanism of inward rectification.
1995,
Pubmed Yasui,
Contribution of potassium accumulation in narrow extracellular spaces to the genesis of nicorandil-induced large inward tail current in guinea-pig ventricular cells.
1993,
Pubmed Zhang,
Gating properties of GIRK channels activated by Galpha(o)- and Galpha(i)-coupled muscarinic m2 receptors in Xenopus oocytes: the role of receptor precoupling in RGS modulation.
2002,
Pubmed
,
Xenbase
