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 Neurosci
2008 Oct 29;2844:11131-40. doi: 10.1523/JNEUROSCI.2763-08.2008.
Show Gene links
Show Anatomy links
Opposite effects of zinc on human and rat P2X2 receptors.
Tittle RK
,
Hume RI
.
???displayArticle.abstract???
P2X(2) receptors from rats show potentiation when a submaximal concentration of ATP is combined with zinc in the range of 10-100 microM. Alignment of the amino acid sequences of human P2X(2) (hP2X(2)) and rat P2X(2) (rP2X(2)) indicated that only one of two histidines essential for zinc potentiation in rP2X(2) is present at the homologous position in hP2X(2) (H132), with the position homologous to rat H213 instead having an arginine (R225). When expressed in Xenopus oocytes, mouse P2X(2a) and P2X(2b) receptors showed zinc potentiation indistinguishable from rat P2X(2a), but hP2X(2b) receptors were inhibited by zinc. The extent of zinc inhibition of hP2X(2b) varied with the ATP concentration, with an IC(50) of 8.4 microM zinc when ATP was applied at 10% of maximal and 87 microM zinc when ATP was applied at 99% of maximal. Site-directed mutagenesis showed that none of the nine histidines in the extracellular domain of hP2X(2b) were required for zinc inhibition, although inhibition was attenuated in the H204A and H209A mutations. Mutating R225 to a cysteine was sufficient to confer zinc potentiation onto hP2X(2b), and zinc potentiation was absent in the hP2X(2b)H132A/R225C double mutant. This suggests that zinc potentiation in the mutant hP2X(2b) uses the same mechanism as zinc potentiation in wild-type rP2X(2a). Because of the species-specific modulation by zinc, evidence for an in vivo role of P2X(2) receptors based on studies conducted on genetically modified mice needs to be viewed with caution when extrapolations are made to the function of the human nervous system.
Auld,
Zinc coordination sphere in biochemical zinc sites.
2001, Pubmed
Auld,
Zinc coordination sphere in biochemical zinc sites.
2001,
Pubmed
Brake,
New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor.
1994,
Pubmed
,
Xenbase
Brändle,
Desensitization of the P2X(2) receptor controlled by alternative splicing.
1997,
Pubmed
,
Xenbase
Burnstock,
Physiology and pathophysiology of purinergic neurotransmission.
2007,
Pubmed
Clyne,
The role of histidine residues in modulation of the rat P2X(2) purinoceptor by zinc and pH.
2002,
Pubmed
,
Xenbase
Clyne,
Mutational analysis of the conserved cysteines of the rat P2X2 purinoceptor.
2002,
Pubmed
,
Xenbase
Clyne,
Expression level dependent changes in the properties of P2X2 receptors.
2003,
Pubmed
,
Xenbase
Cockayne,
P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP.
2005,
Pubmed
Coddou,
Dissecting the facilitator and inhibitor allosteric metal sites of the P2X4 receptor channel: critical roles of CYS132 for zinc potentiation and ASP138 for copper inhibition.
2007,
Pubmed
,
Xenbase
Ding,
Ion permeation and block of P2X(2) purinoceptors: single channel recordings.
1999,
Pubmed
Dunn,
P2X receptors in peripheral neurons.
2001,
Pubmed
Ennion,
Conserved cysteine residues in the extracellular loop of the human P2X(1) receptor form disulfide bonds and are involved in receptor trafficking to the cell surface.
2002,
Pubmed
,
Xenbase
Finger,
ATP signaling is crucial for communication from taste buds to gustatory nerves.
2005,
Pubmed
Frederickson,
The neurobiology of zinc in health and disease.
2005,
Pubmed
Friday,
Contribution of extracellular negatively charged residues to ATP action and zinc modulation of rat P2X2 receptors.
2008,
Pubmed
,
Xenbase
Fujiwara,
Density-dependent changes of the pore properties of the P2X2 receptor channel.
2004,
Pubmed
,
Xenbase
Gever,
Pharmacology of P2X channels.
2006,
Pubmed
Kanjhan,
Allosteric modulation of native cochlear P2X receptors: insights from comparison with recombinant P2X2 receptors.
2003,
Pubmed
,
Xenbase
Kanjhan,
Distribution of the P2X2 receptor subunit of the ATP-gated ion channels in the rat central nervous system.
1999,
Pubmed
King,
Effects of extracellular pH on agonism and antagonism at a recombinant P2X2 receptor.
1997,
Pubmed
,
Xenbase
Koshimizu,
Carboxyl-terminal splicing enhances physical interactions between the cytoplasmic tails of purinergic P2X receptors.
2006,
Pubmed
Laube,
Potentiation of inhibitory glycinergic neurotransmission by Zn2+: a synergistic interplay between presynaptic P2X2 and postsynaptic glycine receptors.
2002,
Pubmed
Laube,
Modulation by zinc ions of native rat and recombinant human inhibitory glycine receptors.
1995,
Pubmed
,
Xenbase
Li,
Zn2+ potentiates excitatory action of ATP on mammalian neurons.
1993,
Pubmed
Li,
Inhibition of ATP-activated current by zinc in dorsal root ganglion neurones of bullfrog.
1997,
Pubmed
Lorca,
Extracellular histidine residues identify common structural determinants in the copper/zinc P2X2 receptor modulation.
2005,
Pubmed
,
Xenbase
Lynch,
Molecular and functional characterization of human P2X(2) receptors.
1999,
Pubmed
,
Xenbase
Nagaya,
An intersubunit zinc binding site in rat P2X2 receptors.
2005,
Pubmed
,
Xenbase
Nakazawa,
Dopamine and 5-hydroxytryptamine selectively potentiate neuronal type ATP receptor channels.
1996,
Pubmed
,
Xenbase
Nakazawa,
pH dependence of facilitation by neurotransmitters and divalent cations of P2X2 purinoceptor/channels.
1997,
Pubmed
,
Xenbase
North,
Molecular physiology of P2X receptors.
2002,
Pubmed
Pankratov,
Vesicular release of ATP at central synapses.
2006,
Pubmed
Paoletti,
High-affinity zinc inhibition of NMDA NR1-NR2A receptors.
1997,
Pubmed
,
Xenbase
Ren,
P2X2 subunits contribute to fast synaptic excitation in myenteric neurons of the mouse small intestine.
2003,
Pubmed
Rong,
Pivotal role of nucleotide P2X2 receptor subunit of the ATP-gated ion channel mediating ventilatory responses to hypoxia.
2003,
Pubmed
Simon,
Localization and functional expression of splice variants of the P2X2 receptor.
1997,
Pubmed
,
Xenbase
Smart,
Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc.
1994,
Pubmed
Tittle,
A histidine scan to probe the flexibility of the rat P2X2 receptor zinc-binding site.
2007,
Pubmed
,
Xenbase
Tokmakov,
Coupled transcription-and-translation in Xenopus oocyte and egg extracts.
2006,
Pubmed
,
Xenbase
Wildman,
Potentiation of ATP-responses at a recombinant P2x2 receptor by neurotransmitters and related substances.
1997,
Pubmed
,
Xenbase
Wildman,
Zn2+ modulation of ATP-responses at recombinant P2X2 receptors and its dependence on extracellular pH.
1998,
Pubmed
,
Xenbase
Zhang,
Accuracies of ancestral amino acid sequences inferred by the parsimony, likelihood, and distance methods.
1997,
Pubmed
Zhong,
Multiple P2X receptors on guinea-pig pelvic ganglion neurons exhibit novel pharmacological properties.
2001,
Pubmed
Zhou,
Two mechanisms for inward rectification of current flow through the purinoceptor P2X2 class of ATP-gated channels.
1998,
Pubmed
,
Xenbase
