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.
Biophys J
2003 Feb 01;842 Pt 1:1399-409. doi: 10.1016/S0006-3495(03)74954-6.
Show Gene links
Show Anatomy links
Single channel analysis of the regulation of GIRK1/GIRK4 channels by protein phosphorylation.
Müllner D
.
???displayArticle.abstract???
G-Protein activated, inwardly rectifying potassium channels (GIRKs) are important effectors of G-protein beta/gamma-subunits, playing essential roles in the humoral regulation of cardiac activity and also in higher brain functions. G-protein activation of channels of the GIRK1/GIRK4 heterooligomeric composition is controlled via phosphorylation by cyclic AMP dependent protein kinase (PKA) and dephosphorylation by protein phosphatase 2A (PP(2)A). To study the molecular mechanism of this unprecedented example of G-protein effector regulation, single channel recordings were performed on isolated patches of plasma membranes of Xenopus laevis oocytes. Our study shows that: (i) The open probability (P(o)) of GIRK1/GIRK4 channels, stimulated by coexpressed m(2)-receptors, was significantly increased upon addition of the catalytic subunit of PKA to the cytosolic face of an isolated membrane patch. (ii) At moderate concentrations of recombinant G(beta1/gamma2), used to activate the channel, P(o) was significantly reduced in patches treated with PP(2)A, when compared to patches with PKA-cs. (iii) Several single channel gating parameters, including modal gating behavior, were significantly different between phosphorylated and dephosphorylated channels, indicating different gating behavior between the two forms of the protein. Most of these changes were, however, not responsible for the marked difference in P(o) at moderate G-protein concentrations. (iv) An increase of the frequency of openings (f(o)) and a reduction of dwell time duration of the channel in the long-lasting C(5) state was responsible for facilitation of GIRK1/GIRK4 channels by protein phosphorylation. Dephosphorylation by PP(2)A led to an increase of G(beta1/gamma2) concentration required for full activation of the channel and hence to a reduction of the apparent affinity of GIRK1/GIRK4 for G(beta1/gamma2). (v) Although possibly not directly the target of protein phosphorylation/dephosphorylation, the last 20 C-terminal amino acids of the GIRK1 subunit are required for the reduction of apparent affinity for the G-protein by PP(2)A, indicating that they constitute an essential part of the off-switch.
Bard,
Single channel studies of inward rectifier potassium channel regulation by muscarinic acetylcholine receptors.
2000, Pubmed,
Xenbase
Bard,
Single channel studies of inward rectifier potassium channel regulation by muscarinic acetylcholine receptors.
2000,
Pubmed
,
Xenbase
Dascal,
Signalling via the G protein-activated K+ channels.
1997,
Pubmed
Dascal,
Atrial G protein-activated K+ channel: expression cloning and molecular properties.
1993,
Pubmed
,
Xenbase
Dascal,
Inhibition of function in Xenopus oocytes of the inwardly rectifying G-protein-activated atrial K channel (GIRK1) by overexpression of a membrane-attached form of the C-terminal tail.
1995,
Pubmed
,
Xenbase
Dobrev,
Molecular basis of downregulation of G-protein-coupled inward rectifying K(+) current (I(K,ACh) in chronic human atrial fibrillation: decrease in GIRK4 mRNA correlates with reduced I(K,ACh) and muscarinic receptor-mediated shortening of action potentials.
2001,
Pubmed
Doupnik,
RGS proteins reconstitute the rapid gating kinetics of gbetagamma-activated inwardly rectifying K+ channels.
1997,
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
Hilgemann,
The complex and intriguing lives of PIP2 with ion channels and transporters.
2001,
Pubmed
Iñiguez-Lluhi,
G protein beta gamma subunits synthesized in Sf9 cells. Functional characterization and the significance of prenylation of gamma.
1992,
Pubmed
Ivanova-Nikolova,
Effector contributions to G beta gamma-mediated signaling as revealed by muscarinic potassium channel gating.
1997,
Pubmed
Ivanova-Nikolova,
Muscarinic K+ channel in the heart. Modal regulation by G protein beta gamma subunits.
1998,
Pubmed
Kim,
Cytoplasmic unsaturated free fatty acids inhibit ATP-dependent gating of the G protein-gated K(+) channel.
2000,
Pubmed
Kim,
Modulation of rat atrial G protein-coupled K+ channel function by phospholipids.
1999,
Pubmed
Kim,
Potassium channels in cardiac cells activated by arachidonic acid and phospholipids.
1989,
Pubmed
Kim,
Beta-adrenergic regulation of the muscarinic-gated K+ channel via cyclic AMP-dependent protein kinase in atrial cells.
1990,
Pubmed
Kim,
Modulation of acetylcholine-activated K+ channel function in rat atrial cells by phosphorylation.
1991,
Pubmed
Kirsch,
Trypsin activation of atrial muscarinic K+ channels.
1989,
Pubmed
Kovoor,
Evaluation of the role of I(KACh) in atrial fibrillation using a mouse knockout model.
2001,
Pubmed
Kozasa,
Purification of recombinant G proteins from Sf9 cells by hexahistidine tagging of associated subunits. Characterization of alpha 12 and inhibition of adenylyl cyclase by alpha z.
1995,
Pubmed
Krapivinsky,
The cardiac inward rectifier K+ channel subunit, CIR, does not comprise the ATP-sensitive K+ channel, IKATP.
1995,
Pubmed
Kubo,
Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel.
1993,
Pubmed
,
Xenbase
Kunkel,
Identification of domains conferring G protein regulation on inward rectifier potassium channels.
1995,
Pubmed
,
Xenbase
Kurachi,
Arachidonic acid metabolites as intracellular modulators of the G protein-gated cardiac K+ channel.
1989,
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
Lohberger,
IK.ACh activation by arachidonic acid occurs via a G-protein-independent pathway mediated by the GIRK1 subunit.
2000,
Pubmed
,
Xenbase
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
Mark,
G-protein mediated gating of inward-rectifier K+ channels.
2000,
Pubmed
,
Xenbase
Medina,
A switch mechanism for G beta gamma activation of I(KACh).
2000,
Pubmed
Müllner,
Heterologous facilitation of G protein-activated K(+) channels by beta-adrenergic stimulation via cAMP-dependent protein kinase.
2000,
Pubmed
,
Xenbase
Nakajima,
Platelet-activating factor activates cardiac GK via arachidonic acid metabolites.
1991,
Pubmed
Nemec,
Gbetagamma binding increases the open time of IKACh: kinetic evidence for multiple Gbetagamma binding sites.
1999,
Pubmed
Peleg,
G(alpha)(i) controls the gating of the G protein-activated K(+) channel, GIRK.
2002,
Pubmed
,
Xenbase
Pessia,
Contributions of the C-terminal domain to gating properties of inward rectifier potassium channels.
1995,
Pubmed
Pleumsamran,
Inhibition of ATP-induced increase in muscarinic K+ current by trypsin, alkaline pH, and anions.
1998,
Pubmed
Ramos-Franco,
Platelet-activating factor receptor-dependent activation of the muscarinic K+ current in bullfrog atrial myocytes.
1993,
Pubmed
Saitoh,
RGS8 accelerates G-protein-mediated modulation of K+ currents.
1997,
Pubmed
,
Xenbase
Scherer,
Arachidonic acid metabolites alter G protein-mediated signal transduction in heart. Effects on muscarinic K+ channels.
1990,
Pubmed
Scherer,
Leukotriene C4 modulation of muscarinic K+ current activation in bullfrog atrial myocytes.
1993,
Pubmed
Schreibmayer,
Inhibition of an inwardly rectifying K+ channel by G-protein alpha-subunits.
1996,
Pubmed
,
Xenbase
Silverman,
Subunit stoichiometry of a heteromultimeric G protein-coupled inward-rectifier K+ channel.
1996,
Pubmed
,
Xenbase
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
Wickman,
Abnormal heart rate regulation in GIRK4 knockout mice.
1998,
Pubmed
Yakubovich,
Slow modal gating of single G protein-activated K+ channels expressed in Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Yamada,
G protein regulation of potassium ion channels.
1998,
Pubmed
Yatani,
Detergents, dimeric G beta gamma, and eicosanoid pathways to muscarinic atrial K+ channels.
1990,
Pubmed
