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Proc Natl Acad Sci U S A
1998 Feb 03;953:1307-12. doi: 10.1073/pnas.95.3.1307.
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Activation of the atrial KACh channel by the betagamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates.
Sui JL, Petit-Jacques J, Logothetis DE.
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The betagamma subunits of GTP-binding proteins (Gbetagamma) activate the muscarinic K+ channel (KACh) in heart by direct binding to both of its component subunits. KACh channels can also be gated by internal Na+ ions. Both activation mechanisms show dependence on hydrolysis of intracellular ATP. We report that phosphatidylinositol 4,5-bisphosphate (PIP2) mimics the ATP effects and that depletion or block of PIP2 retards the stimulatory effects of Gbetagamma subunits or Na+ ions on channel activity, effects that can be reversed by restoring PIP2. Thus, regulation of KACh channel activity may be crucially dependent on PIP2 and phosphatidylinositol signaling. These striking functional results are in agreement with in vitro biochemical studies on the PIP2 requirement for Gbetagamma stimulation of G protein receptor kinase activity, thus implicating phosphatidylinositol phospholipids as a potential control point for Gbetagamma-mediated signal transduction.
Armstrong,
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Armstrong,
Ion channel regulation. Introduction.
1999,
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1996,
Pubmed
,
Xenbase DebBurman,
G protein-coupled receptor kinase GRK2 is a phospholipid-dependent enzyme that can be conditionally activated by G protein betagamma subunits.
1996,
Pubmed DebBurman,
Lipid-mediated regulation of G protein-coupled receptor kinases 2 and 3.
1995,
Pubmed Doupnik,
Time resolved kinetics of direct G beta 1 gamma 2 interactions with the carboxyl terminus of Kir3.4 inward rectifier K+ channel subunits.
1996,
Pubmed
,
Xenbase Fan,
Anionic phospholipids activate ATP-sensitive potassium channels.
1997,
Pubmed Fukami,
Identification of a phosphatidylinositol 4,5-bisphosphate-binding site in chicken skeletal muscle alpha-actinin.
1996,
Pubmed Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed Harlan,
Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate.
1994,
Pubmed Heidbüchel,
ATP-dependent activation of atrial muscarinic K+ channels in the absence of agonist and G-nucleotides.
1990,
Pubmed Hilgemann,
Cytoplasmic ATP-dependent regulation of ion transporters and channels: mechanisms and messengers.
1997,
Pubmed Hilgemann,
Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2.
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,
Binding of the G protein betagamma subunit to multiple regions of G protein-gated inward-rectifying K+ channels.
1997,
Pubmed Inanobe,
G beta gamma directly binds to the carboxyl terminus of the G protein-gated muscarinic K+ channel, GIRK1.
1995,
Pubmed Kim,
G-protein beta gamma-subunits activate the cardiac muscarinic K+-channel via phospholipase A2.
1989,
Pubmed Kim,
Modulation of acetylcholine-activated K+ channel function in rat atrial cells by phosphorylation.
1991,
Pubmed Krapivinsky,
G beta gamma binds directly to the G protein-gated K+ channel, IKACh.
1995,
Pubmed Krapivinsky,
The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins.
1995,
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 Logothetis,
Incremental reductions of positive charge within the S4 region of a voltage-gated K+ channel result in corresponding decreases in gating charge.
1992,
Pubmed
,
Xenbase Logothetis,
The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart.
,
Pubmed Mayer,
A putative modular domain present in diverse signaling proteins.
1993,
Pubmed Methfessel,
Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels.
1986,
Pubmed
,
Xenbase Pertile,
Phosphatidylinositol 4,5-bisphosphate synthesis is required for activation of phospholipase D in U937 cells.
1995,
Pubmed Pitcher,
Pleckstrin homology domain-mediated membrane association and activation of the beta-adrenergic receptor kinase requires coordinate interaction with G beta gamma subunits and lipid.
1995,
Pubmed Pitcher,
Phosphatidylinositol 4,5-bisphosphate (PIP2)-enhanced G protein-coupled receptor kinase (GRK) activity. Location, structure, and regulation of the PIP2 binding site distinguishes the GRK subfamilies.
1996,
Pubmed Reuveny,
Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits.
1994,
Pubmed
,
Xenbase Silverman,
Subunit stoichiometry of a heteromultimeric G protein-coupled inward-rectifier K+ channel.
1996,
Pubmed
,
Xenbase Soejima,
Mode of regulation of the ACh-sensitive K-channel by the muscarinic receptor in rabbit atrial cells.
1984,
Pubmed Stühmer,
Electrophysiological recording from Xenopus oocytes.
1992,
Pubmed
,
Xenbase Sui,
Na+ activation of the muscarinic K+ channel by a G-protein-independent mechanism.
1996,
Pubmed
,
Xenbase Touhara,
Binding of G protein beta gamma-subunits to pleckstrin homology domains.
1994,
Pubmed Tsukada,
Binding of beta gamma subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase.
1994,
Pubmed Vivaudou,
Skeletal muscle ATP-sensitive K+ channels recorded from sarcolemmal blebs of split fibers: ATP inhibition is reduced by magnesium and ADP.
1991,
Pubmed Yao,
The pleckstrin homology domain of Bruton tyrosine kinase interacts with protein kinase C.
1994,
Pubmed
