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New roles for RGS2, 5 and 8 on the ratio-dependent modulation of recombinant GIRK channels expressed in Xenopus oocytes.
Herlitze S, Ruppersberg JP, Mark MD.
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1. The activation of G protein-regulated inward rectifying potassium (GIRK) channels is modulated by G protein-coupled receptors (GPCRs) via the G protein betagamma subunits and is accelerated by regulators of G protein signalling (RGS). In the present study we investigated the ratio dependence of receptor-mediated activation and deactivation and the influence of new members of the RGS protein family on GIRK currents by coexpressing the recombinant protein subunits in Xenopus oocytes and further analysis of the whole cell currents. 2. The activation of GIRK channels by the muscarinic acetylcholine receptor M2 (M2 mAChR) is strongly dependent on the ratio of receptor to channel in Xenopus oocytes. The increase and on-rate of the amplified current is affected by this ratio. An excess of receptor over channel is necessary for current amplification, while the reverse excess of channel over receptor abolishes the effect. 3. The speed of receptor-mediated activation of GIRK currents is accelerated for a high ratio of receptor to channel, while the time of deactivation is independent of this ratio. 4. Coexpression of RGS2, 5 and 8 accelerates the speed for ACh-mediated activation and deactivation of GIRK1/2 and GIRK1/4 currents. Thereby the receptor/channel/RGS ratio determines the amount of current amplification. 5. Bordetella pertussis toxin completely abolished ACh-mediated current amplification of GIRK channels coexpressed with or without RGS2. 6. Two single point mutations in the RGS2 protein (RGS2(N109S) and RGS2(L180F)) reduced the acceleration of current amplification after ACh application on GIRK1/4 channels compared with RGS2 wild-type protein.
Berman,
Mammalian RGS proteins: barbarians at the gate.
1998, Pubmed
Berman,
Mammalian RGS proteins: barbarians at the gate.
1998,
Pubmed Breitwieser,
Mechanisms of K+ channel regulation.
1996,
Pubmed Breitwieser,
Uncoupling of cardiac muscarinic and beta-adrenergic receptors from ion channels by a guanine nucleotide analogue.
,
Pubmed Bünemann,
Regulators of G protein signaling (RGS) proteins constitutively activate Gbeta gamma-gated potassium channels.
1998,
Pubmed Bünemann,
In vivo downregulation of M2 receptors revealed by measurement of muscarinic K+ current in cultured guinea-pig atrial myocytes.
1997,
Pubmed Chuang,
Evidence that the nucleotide exchange and hydrolysis cycle of G proteins causes acute desensitization of G-protein gated inward rectifier K+ channels.
1998,
Pubmed Dascal,
Atrial G protein-activated K+ channel: expression cloning and molecular properties.
1993,
Pubmed
,
Xenbase Dohlman,
RGS proteins and signaling by heterotrimeric G proteins.
1997,
Pubmed Doupnik,
RGS proteins reconstitute the rapid gating kinetics of gbetagamma-activated inwardly rectifying K+ channels.
1997,
Pubmed
,
Xenbase Druey,
Inhibition of regulator of G protein signaling function by two mutant RGS4 proteins.
1997,
Pubmed Duprat,
Heterologous multimeric assembly is essential for K+ channel activity of neuronal and cardiac G-protein-activated inward rectifiers.
1995,
Pubmed
,
Xenbase Hedin,
Cloning of a Xenopus laevis inwardly rectifying K+ channel subunit that permits GIRK1 expression of IKACh currents in oocytes.
1996,
Pubmed
,
Xenbase Herlitze,
A general and rapid mutagenesis method using polymerase chain reaction.
1990,
Pubmed Heximer,
RGS2/G0S8 is a selective inhibitor of Gqalpha function.
1997,
Pubmed Ho,
Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
1989,
Pubmed Hosoya,
A functional model for G protein activation of the muscarinic K+ channel in guinea pig atrial myocytes. Spectral analysis of the effect of GTP on single-channel kinetics.
1996,
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,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase Iizuka,
Localization of a G-protein-coupled inwardly rectifying K+ channel, CIR, in the rat brain.
1997,
Pubmed Ingi,
Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity.
1998,
Pubmed Jan,
Voltage-gated and inwardly rectifying potassium channels.
1997,
Pubmed Karschin,
IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain.
1996,
Pubmed Kim,
ATP-dependent regulation of a G protein-coupled K+ channel (GIRK1/GIRK4) expressed in oocytes.
1997,
Pubmed
,
Xenbase Koelle,
A new family of G-protein regulators - the RGS proteins.
1997,
Pubmed Kofuji,
Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells.
1996,
Pubmed
,
Xenbase Kofuji,
Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers.
1995,
Pubmed
,
Xenbase Krapivinsky,
The cardiac inward rectifier K+ channel subunit, CIR, does not comprise the ATP-sensitive K+ channel, IKATP.
1995,
Pubmed Krapivinsky,
The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins.
1995,
Pubmed
,
Xenbase Kubo,
Primary structure and functional expression of a mouse inward rectifier potassium channel.
1993,
Pubmed
,
Xenbase Kurachi,
G protein regulation of cardiac muscarinic potassium channel.
1995,
Pubmed Lesage,
Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels.
1995,
Pubmed
,
Xenbase 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 Luchian,
A C-terminal peptide of the GIRK1 subunit directly blocks the G protein-activated K+ channel (GIRK) expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase Murer,
An immunocytochemical study on the distribution of two G-protein-gated inward rectifier potassium channels (GIRK2 and GIRK4) in the adult rat brain.
1997,
Pubmed Nair,
Cardiac muscarinic potassium channel activity is attenuated by inhibitors of G beta gamma.
1995,
Pubmed Neer,
Intracellular signalling: turning down G-protein signals.
1997,
Pubmed Pfaffinger,
GTP-binding proteins couple cardiac muscarinic receptors to a K channel.
,
Pubmed Reuveny,
Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits.
1994,
Pubmed
,
Xenbase Saitoh,
RGS8 accelerates G-protein-mediated modulation of K+ currents.
1997,
Pubmed
,
Xenbase Sakmann,
Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart.
,
Pubmed Schreibmayer,
Inhibition of an inwardly rectifying K+ channel by G-protein alpha-subunits.
1996,
Pubmed
,
Xenbase Siderovski,
A new family of regulators of G-protein-coupled receptors?
1996,
Pubmed Slesinger,
Defective gamma-aminobutyric acid type B receptor-activated inwardly rectifying K+ currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice.
1997,
Pubmed
,
Xenbase Snow,
GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain.
1998,
Pubmed Soejima,
Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells.
1984,
Pubmed Sui,
Activation of the atrial KACh channel by the betagamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates.
1998,
Pubmed
,
Xenbase Tesmer,
Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis.
1997,
Pubmed Tu,
Inhibition of brain Gz GAP and other RGS proteins by palmitoylation of G protein alpha subunits.
1997,
Pubmed Wickman,
Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel.
1994,
Pubmed Zerangue,
G-protein signaling: fine-tuning signaling kinetics.
1998,
Pubmed
