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
2006 Oct 01;576Pt 1:135-49. doi: 10.1113/jphysiol.2006.115246.
Show Gene links
Show Anatomy links
Regulation of the desensitization and ion selectivity of ATP-gated P2X2 channels by phosphoinositides.
Fujiwara Y
,
Kubo Y
.
???displayArticle.abstract???
Phosphoinositides (PIP(n)s) are known to regulate the activity of some ion channels. Here we determined that ATP-gated P2X(2) channels also are regulated by PIP(n)s, and investigated the structural background and the unique features of this regulation. We initially used two-electrode voltage clamp to analyse the electrophysiological properties of P2X(2) channels expressed in Xenopus oocytes, and observed that preincubation with wortmannin or LY294002, two PI3K inhibitors, accelerated channel desensitization. K365Q or K369Q mutation of the conserved, positively charged, amino acid residues in the proximal region of the cytoplasmic C-terminal domain also accelerated desensitization, whereas a K365R or K369R mutation did not. We observed that the permeability of the channel to N-methyl-d-glucamine (NMDG) transiently increased and then decreased after ATP application, and that the speed of the decrease was accelerated by K365Q or K369Q mutation or PI3K inhibition. Using GST-tagged recombinant proteins spanning the proximal C-terminal region, we then analysed their binding of the P2X(2) cytoplasmic domain to anionic lipids using PIP(n)s-coated nitrocellulose membranes. We found that the recombinant proteins that included the positively charged region bound to PIPs and PIP(2)s, and that this binding was eliminated by the K365Q and K369Q mutations. We also used a fluorescence assay to confirm that fusion proteins comprising the proximal C-terminal region of P2X(2) with EGFP expressed in COS-7 cells closely associated with the membrane. Taken together, these results show that membrane-bound PIP(n)s play a key role in maintaining channel activity and regulating pore dilation through electrostatic interaction with the proximal region of the P2X(2) cytoplasmic C-terminal domain.
Baukrowitz,
PIP2 and PIP as determinants for ATP inhibition of KATP channels.
1998, Pubmed,
Xenbase
Baukrowitz,
PIP2 and PIP as determinants for ATP inhibition of KATP channels.
1998,
Pubmed
,
Xenbase
Bichet,
Evolving potassium channels by means of yeast selection reveals structural elements important for selectivity.
2004,
Pubmed
,
Xenbase
Brake,
New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor.
1994,
Pubmed
,
Xenbase
Chaumont,
Identification of a trafficking motif involved in the stabilization and polarization of P2X receptors.
2004,
Pubmed
Chemin,
A phospholipid sensor controls mechanogating of the K+ channel TREK-1.
2005,
Pubmed
Collo,
Cloning OF P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels.
1996,
Pubmed
Corvera,
Phosphatidylinositol 3-kinase and the control of endosome dynamics: new players defined by structural motifs.
2001,
Pubmed
Czirják,
Inhibition of TASK-1 potassium channel by phospholipase C.
2001,
Pubmed
,
Xenbase
Ding,
Inactivation of P2X2 purinoceptors by divalent cations.
2000,
Pubmed
Donaldson,
PIP2 binding residues of Kir2.1 are common targets of mutations causing Andersen syndrome.
2003,
Pubmed
Eickhorst,
Control of P2X(2) channel permeability by the cytosolic domain.
2002,
Pubmed
,
Xenbase
Fisher,
Time-resolved measurement of state-specific P2X2 ion channel cytosolic gating motions.
2004,
Pubmed
Fujiwara,
Density-dependent changes of the pore properties of the P2X2 receptor channel.
2004,
Pubmed
,
Xenbase
Fujiwara,
Ser165 in the second transmembrane region of the Kir2.1 channel determines its susceptibility to blockade by intracellular Mg2+.
2002,
Pubmed
,
Xenbase
Hardie,
Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors.
2001,
Pubmed
Hilgemann,
The complex and intriguing lives of PIP2 with ion channels and transporters.
2001,
Pubmed
Huang,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase
Inoue,
ATP- and adenosine-mediated signaling in the central nervous system: chronic pain and microglia: involvement of the ATP receptor P2X4.
2004,
Pubmed
Jiang,
N-methyl-D-glucamine and propidium dyes utilize different permeation pathways at rat P2X(7) receptors.
2005,
Pubmed
Khakh,
Allosteric control of gating and kinetics at P2X(4) receptor channels.
1999,
Pubmed
,
Xenbase
Khakh,
Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds.
1999,
Pubmed
Khakh,
Dynamic selectivity filters in ion channels.
1999,
Pubmed
Khakh,
Contribution of transmembrane regions to ATP-gated P2X2 channel permeability dynamics.
2005,
Pubmed
Koshimizu,
Contributions of the C-terminal domain to the control of P2X receptor desensitization.
1999,
Pubmed
Lewis,
Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons.
1995,
Pubmed
Liou,
Regulation of ROMK1 channel by protein kinase A via a phosphatidylinositol 4,5-bisphosphate-dependent mechanism.
1999,
Pubmed
,
Xenbase
Lopes,
Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
2002,
Pubmed
,
Xenbase
Minor,
The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel.
2000,
Pubmed
,
Xenbase
North,
Molecular physiology of P2X receptors.
2002,
Pubmed
Oliver,
Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.
2004,
Pubmed
,
Xenbase
Pochynyuk,
Identification of a functional phosphatidylinositol 3,4,5-trisphosphate binding site in the epithelial Na+ channel.
2005,
Pubmed
Prestwich,
Phosphoinositide signaling; from affinity probes to pharmaceutical targets.
2004,
Pubmed
Ralevic,
Receptors for purines and pyrimidines.
1998,
Pubmed
Schulte,
pH gating of ROMK (K(ir)1.1) channels: control by an Arg-Lys-Arg triad disrupted in antenatal Bartter syndrome.
1999,
Pubmed
Séguéla,
A novel neuronal P2x ATP receptor ion channel with widespread distribution in the brain.
1996,
Pubmed
,
Xenbase
Shyng,
Membrane phospholipid control of nucleotide sensitivity of KATP channels.
1998,
Pubmed
Smith,
Identification of amino acids within the P2X2 receptor C-terminus that regulate desensitization.
1999,
Pubmed
,
Xenbase
Srivastava,
The phosphatidylinositol 3-phosphate phosphatase myotubularin- related protein 6 (MTMR6) is a negative regulator of the Ca2+-activated K+ channel KCa3.1.
2005,
Pubmed
Suh,
Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis.
2002,
Pubmed
Surprenant,
The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7).
1996,
Pubmed
Toker,
The synthesis and cellular roles of phosphatidylinositol 4,5-bisphosphate.
1998,
Pubmed
Valera,
A new class of ligand-gated ion channel defined by P2x receptor for extracellular ATP.
1994,
Pubmed
,
Xenbase
Vanhaesebroeck,
Synthesis and function of 3-phosphorylated inositol lipids.
2001,
Pubmed
Virginio,
Pore dilation of neuronal P2X receptor channels.
1999,
Pubmed
Weiner,
A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity.
2002,
Pubmed
Werner,
Domains of P2X receptors involved in desensitization.
1996,
Pubmed
,
Xenbase
Wu,
Dual regulation of voltage-gated calcium channels by PtdIns(4,5)P2.
2002,
Pubmed
,
Xenbase
Zhainazarov,
Modulation of the olfactory CNG channel by Ptdlns(3,4,5)P3.
2004,
Pubmed
Zhang,
PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.
2003,
Pubmed
,
Xenbase
Zhou,
Two mechanisms for inward rectification of current flow through the purinoceptor P2X2 class of ATP-gated channels.
1998,
Pubmed
,
Xenbase
Zhou,
Identification of a site that modifies desensitization of P2X2 receptors.
1998,
Pubmed
,
Xenbase
