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 Jan 15;570Pt 2:339-54. doi: 10.1113/jphysiol.2005.095810.
Show Gene links
Show Anatomy links
The receptor site of the spider toxin PcTx1 on the proton-gated cation channel ASIC1a.
Salinas M, Rash LD, Baron A, Lambeau G, Escoubas P, Lazdunski M.
???displayArticle.abstract???
Acid-sensing ion channels (ASICs) are excitatory neuronal cation channels, involved in physiopathological processes related to extracellular pH fluctuation such as nociception, ischaemia, perception of sour taste and synaptic transmission. The spider peptide toxin psalmotoxin 1 (PcTx1) has previously been shown to inhibit specifically the proton-gated cation channel ASIC1a. To identify the binding site of PcTx1, we produced an iodinated form of the toxin ((125)I-PcTx1Y(N)) and developed a set of binding and electrophysiological experiments on several chimeras of ASIC1a and the PcTx1-insensitive channels ASIC1b and ASIC2a. We show that (125)I-PcTx1Y(N) binds specifically to ASIC1a at a single site, with an IC(50) of 128 pM, distinct from the amiloride blocking site. Results obtained from chimeras indicate that PcTx1 does not bind to ASIC1a transmembrane domains (M1 and M2), involved in formation of the ion pore, but binds principally on both cysteine-rich domains I and II (CRDI and CRDII) of the extracellular loop. The post-M1 and pre-M2 regions, although not involved in the binding site, are crucial for the ability of PcTx1 to inhibit ASIC1a current. The linker domain between CRDI and CRDII is important for their correct spatial positioning to form the PcTx1 binding site. These results will be useful for the future identification or design of new molecules acting on ASICs.
Babini,
Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1).
2002, Pubmed,
Xenbase
Babini,
Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1).
2002,
Pubmed
,
Xenbase Baron,
Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1.
2002,
Pubmed Baron,
ASIC-like, proton-activated currents in rat hippocampal neurons.
2002,
Pubmed Baron,
Zn2+ and H+ are coactivators of acid-sensing ion channels.
2001,
Pubmed
,
Xenbase Bässler,
Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b.
2001,
Pubmed
,
Xenbase Benson,
Acid-evoked currents in cardiac sensory neurons: A possible mediator of myocardial ischemic sensation.
1999,
Pubmed Biagini,
Regional and subunit-specific downregulation of acid-sensing ion channels in the pilocarpine model of epilepsy.
2001,
Pubmed Bianchi,
Protons at the gate: DEG/ENaC ion channels help us feel and remember.
2002,
Pubmed Bourinet,
Interaction of SNX482 with domains III and IV inhibits activation gating of alpha(1E) (Ca(V)2.3) calcium channels.
2001,
Pubmed Bubien,
Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin 1.
2004,
Pubmed Canessa,
Epithelial sodium channel related to proteins involved in neurodegeneration.
1993,
Pubmed
,
Xenbase Canessa,
Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.
1994,
Pubmed
,
Xenbase Catarsi,
Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF.
2001,
Pubmed
,
Xenbase Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
Pubmed Champigny,
Mutations causing neurodegeneration in Caenorhabditis elegans drastically alter the pH sensitivity and inactivation of the mammalian H+-gated Na+ channel MDEG1.
1998,
Pubmed
,
Xenbase Chen,
The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity.
2005,
Pubmed
,
Xenbase Chen,
A sensory neuron-specific, proton-gated ion channel.
1998,
Pubmed Chen,
A role for ASIC3 in the modulation of high-intensity pain stimuli.
2002,
Pubmed Chu,
Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels.
2004,
Pubmed Coric,
Proton sensitivity of ASIC1 appeared with the rise of fishes by changes of residues in the region that follows TM1 in the ectodomain of the channel.
2005,
Pubmed Coric,
The extracellular domain determines the kinetics of desensitization in acid-sensitive ion channel 1.
2003,
Pubmed
,
Xenbase Coscoy,
The Phe-Met-Arg-Phe-amide-activated sodium channel is a tetramer.
1998,
Pubmed
,
Xenbase Cottrell,
Location of a ligand recognition site of FMRFamide-gated Na(+) channels.
2001,
Pubmed
,
Xenbase Deval,
Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability.
2003,
Pubmed Diochot,
A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons.
2004,
Pubmed
,
Xenbase Diochot,
Sea anemone peptides with a specific blocking activity against the fast inactivating potassium channel Kv3.4.
1998,
Pubmed
,
Xenbase Escoubas,
Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels.
2003,
Pubmed Escoubas,
Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels.
2000,
Pubmed
,
Xenbase Ettaiche,
Acid-sensing ion channel 2 is important for retinal function and protects against light-induced retinal degeneration.
2004,
Pubmed Firsov,
Mutational analysis of cysteine-rich domains of the epithelium sodium channel (ENaC). Identification of cysteines essential for channel expression at the cell surface.
1999,
Pubmed
,
Xenbase Firsov,
The heterotetrameric architecture of the epithelial sodium channel (ENaC).
1998,
Pubmed
,
Xenbase Frénal,
Exploring structural features of the interaction between the scorpion toxinCnErg1 and ERG K+ channels.
2004,
Pubmed Gründer,
Identification of a highly conserved sequence at the N-terminus of the epithelial Na+ channel alpha subunit involved in gating.
1999,
Pubmed
,
Xenbase Gründer,
A new member of acid-sensing ion channels from pituitary gland.
2000,
Pubmed
,
Xenbase Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed Ho,
Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
1989,
Pubmed Hong,
A transmembrane domain of the putative channel subunit MEC-4 influences mechanotransduction and neurodegeneration in C. elegans.
1994,
Pubmed
,
Xenbase Huang,
Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans.
1994,
Pubmed HUNTER,
Preparation of iodine-131 labelled human growth hormone of high specific activity.
1962,
Pubmed Immke,
Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade.
2003,
Pubmed Immke,
Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons.
2001,
Pubmed Ji,
Point mutations in the post-M2 region of human alpha-ENaC regulate cation selectivity.
2001,
Pubmed
,
Xenbase Jones,
Acid-induced pain and its modulation in humans.
2004,
Pubmed Kellenberger,
Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure.
2002,
Pubmed Kellenberger,
A single point mutation in the pore region of the epithelial Na+ channel changes ion selectivity by modifying molecular sieving.
1999,
Pubmed
,
Xenbase Kress,
Capsaicin, protons and heat: new excitement about nociceptors.
1999,
Pubmed Krishtal,
The ASICs: signaling molecules? Modulators?
2003,
Pubmed Lambeau,
Identification and properties of very high affinity brain membrane-binding sites for a neurotoxic phospholipase from the taipan venom.
1989,
Pubmed Lin,
Acid-activated cation currents in rat vallate taste receptor cells.
2002,
Pubmed Lingueglia,
Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel.
1995,
Pubmed
,
Xenbase Lingueglia,
Expression cloning of an epithelial amiloride-sensitive Na+ channel. A new channel type with homologies to Caenorhabditis elegans degenerins.
1993,
Pubmed
,
Xenbase Lingueglia,
A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells.
1997,
Pubmed Liu,
Acidic stimuli activates two distinct pathways in taste receptor cells from rat fungiform papillae.
2001,
Pubmed McCleskey,
Ion channels of nociception.
1999,
Pubmed Page,
The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function.
2004,
Pubmed Pan,
Role of protons in activation of cardiac sympathetic C-fibre afferents during ischaemia in cats.
1999,
Pubmed Paukert,
Identification of the Ca2+ blocking site of acid-sensing ion channel (ASIC) 1: implications for channel gating.
2004,
Pubmed
,
Xenbase Perry,
Neuronal expression of an FMRFamide-gated Na+ channel and its modulation by acid pH.
2001,
Pubmed Poët,
Exploration of the pore structure of a peptide-gated Na+ channel.
2001,
Pubmed
,
Xenbase Poirot,
Selective regulation of acid-sensing ion channel 1 by serine proteases.
2004,
Pubmed
,
Xenbase Price,
The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice.
2001,
Pubmed Price,
The mammalian sodium channel BNC1 is required for normal touch sensation.
2000,
Pubmed Rehm,
Purification and subunit structure of a putative K+-channel protein identified by its binding properties for dendrotoxin I.
1988,
Pubmed Renard,
Biochemical analysis of the membrane topology of the amiloride-sensitive Na+ channel.
1994,
Pubmed
,
Xenbase Saugstad,
Analysis of the membrane topology of the acid-sensing ion channel 2a.
2004,
Pubmed Schild,
Identification of amino acid residues in the alpha, beta, and gamma subunits of the epithelial sodium channel (ENaC) involved in amiloride block and ion permeation.
1997,
Pubmed
,
Xenbase Sutherland,
Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons.
2001,
Pubmed Tavernarakis,
Caenorhabditis elegans degenerins and vertebrate ENaC ion channels contain an extracellular domain related to venom neurotoxins.
2000,
Pubmed Ugawa,
Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors.
2002,
Pubmed
,
Xenbase Voilley,
Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors.
2001,
Pubmed Waldmann,
The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans.
1996,
Pubmed Waldmann,
A proton-gated cation channel involved in acid-sensing.
1997,
Pubmed
,
Xenbase Waldmann,
H(+)-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels.
1998,
Pubmed Waldmann,
Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons.
1997,
Pubmed Wemmie,
The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
2002,
Pubmed Xie,
ASIC3 and ASIC1 mediate FMRFamide-related peptide enhancement of H+-gated currents in cultured dorsal root ganglion neurons.
2003,
Pubmed Xiong,
Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.
2004,
Pubmed Yermolaieva,
Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a.
2004,
Pubmed
