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
2011 Jun 29;3126:9723-34. doi: 10.1523/JNEUROSCI.1665-11.2011.
Show Gene links
Show Anatomy links
Heteromeric acid-sensing ion channels (ASICs) composed of ASIC2b and ASIC1a display novel channel properties and contribute to acidosis-induced neuronal death.
Sherwood TW
,
Lee KG
,
Gormley MG
,
Askwith CC
.
???displayArticle.abstract???
Acid-sensing ion channel (ASIC) subunits associate to form homomeric or heteromeric proton-gated ion channels in neurons throughout the nervous system. The ASIC1a subunit plays an important role in establishing the kinetics of proton-gated currents in the CNS, and activation of ASIC1a homomeric channels induces neuronal death after local acidosis that accompanies cerebral ischemia. The ASIC2b subunit is expressed in the brain in a pattern that overlaps ASIC1a, yet the contribution of ASIC2b has remained elusive. We find that coexpression of ASIC2b with ASIC1a in Xenopus oocytes results in novel proton-gated currents with properties distinct from ASIC1a homomeric channels. In particular, ASIC2b/1a heteromeric channels are inhibited by the nonselective potassium channel blockers tetraethylammonium and barium. In addition, steady-state desensitization is induced at more basic pH values, and Big Dynorphin sensitivity is enhanced in these unique heteromeric channels. Cultured hippocampal neurons show proton-gated currents consistent with ASIC2b contribution, and these currents are lacking in neurons from mice with an ACCN1 (ASIC2) gene disruption. Finally, we find that these ASIC2b/1a heteromeric channels contribute to acidosis-induced neuronal death. Together, our results show that ASIC2b confers unique properties to heteromeric channels in central neurons. Furthermore, these data indicate that ASIC2, like ASIC1, plays a role in acidosis-induced neuronal death and implicate the ASIC2b/1a subtype as a novel pharmacological target to prevent neuronal injury after stroke.
Adams,
Tetraethylammonium block of the BNC1 channel.
1999, Pubmed,
Xenbase
Adams,
Tetraethylammonium block of the BNC1 channel.
1999,
Pubmed
,
Xenbase
Arias,
Amiloride is neuroprotective in an MPTP model of Parkinson's disease.
2008,
Pubmed
Askwith,
Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons.
2004,
Pubmed
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,
Zn2+ and H+ are coactivators of acid-sensing ion channels.
2001,
Pubmed
,
Xenbase
Baron,
ASIC-like, proton-activated currents in rat hippocampal neurons.
2002,
Pubmed
Bassilana,
The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties.
1997,
Pubmed
,
Xenbase
Benson,
Acid-evoked currents in cardiac sensory neurons: A possible mediator of myocardial ischemic sensation.
1999,
Pubmed
Bernardinelli,
Association between the ACCN1 gene and multiple sclerosis in Central East Sardinia.
2007,
Pubmed
Bässler,
Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b.
2001,
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,
Interaction of acid-sensing ion channel (ASIC) 1 with the tarantula toxin psalmotoxin 1 is state dependent.
2006,
Pubmed
,
Xenbase
Chu,
Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels.
2004,
Pubmed
Chu,
ASIC1a-specific modulation of acid-sensing ion channels in mouse cortical neurons by redox reagents.
2006,
Pubmed
Coryell,
Restoring Acid-sensing ion channel-1a in the amygdala of knock-out mice rescues fear memory but not unconditioned fear responses.
2008,
Pubmed
Coryell,
Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in depression-related behavior.
2009,
Pubmed
Coscoy,
The pre-transmembrane 1 domain of acid-sensing ion channels participates in the ion pore.
1999,
Pubmed
Deval,
ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1.
2004,
Pubmed
Duan,
Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis.
2011,
Pubmed
Duggan,
The PDZ domain protein PICK1 and the sodium channel BNaC1 interact and localize at mechanosensory terminals of dorsal root ganglion neurons and dendrites of central neurons.
2002,
Pubmed
Dwyer,
Acid sensing ion channel (ASIC) inhibitors exhibit anxiolytic-like activity in preclinical pharmacological models.
2009,
Pubmed
Eaton,
Effects of barium on the potassium conductance of squid axon.
1980,
Pubmed
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
Friese,
Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system.
2007,
Pubmed
Gao,
Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons.
2004,
Pubmed
Gao,
Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death.
2005,
Pubmed
Gonzales,
Pore architecture and ion sites in acid-sensing ion channels and P2X receptors.
2009,
Pubmed
Grégoire,
Differential involvement of ASIC1a in the basolateral amygdala in fear memory and unconditioned fear responses.
2009,
Pubmed
Harris,
A permanent ion binding site located between two gates of the Shaker K+ channel.
1998,
Pubmed
,
Xenbase
Heginbotham,
The aromatic binding site for tetraethylammonium ion on potassium channels.
1992,
Pubmed
Hesselager,
pH Dependency and desensitization kinetics of heterologously expressed combinations of acid-sensing ion channel subunits.
2004,
Pubmed
Hoagland,
Identification of a calcium permeable human acid-sensing ion channel 1 transcript variant.
2010,
Pubmed
,
Xenbase
Hruska-Hageman,
Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel).
2002,
Pubmed
Hurst,
External barium block of Shaker potassium channels: evidence for two binding sites.
1995,
Pubmed
,
Xenbase
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Jiang,
Characterization of acid-sensing ion channels in medium spiny neurons of mouse striatum.
2009,
Pubmed
Jiang,
The barium site in a potassium channel by x-ray crystallography.
2000,
Pubmed
Lingueglia,
A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells.
1997,
Pubmed
Mazzuca,
A tarantula peptide against pain via ASIC1a channels and opioid mechanisms.
2007,
Pubmed
Peng,
Acid-sensing ion channel 2 contributes a major component to acid-evoked excitatory responses in spiral ganglion neurons and plays a role in noise susceptibility of mice.
2004,
Pubmed
Pignataro,
Prolonged activation of ASIC1a and the time window for neuroprotection in cerebral ischaemia.
2007,
Pubmed
Price,
Cloning and expression of a novel human brain Na+ channel.
1996,
Pubmed
,
Xenbase
Price,
The mammalian sodium channel BNC1 is required for normal touch sensation.
2000,
Pubmed
Salinas,
The receptor site of the spider toxin PcTx1 on the proton-gated cation channel ASIC1a.
2006,
Pubmed
,
Xenbase
Sherwood,
Dynorphin opioid peptides enhance acid-sensing ion channel 1a activity and acidosis-induced neuronal death.
2009,
Pubmed
,
Xenbase
Taglialatela,
Patterns of internal and external tetraethylammonium block in four homologous K+ channels.
1991,
Pubmed
,
Xenbase
Ugawa,
Amiloride-insensitive currents of the acid-sensing ion channel-2a (ASIC2a)/ASIC2b heteromeric sour-taste receptor channel.
2003,
Pubmed
,
Xenbase
Vergo,
Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model.
2011,
Pubmed
Voilley,
Acid-sensing ion channels (ASICs): new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs).
2004,
Pubmed
Waldmann,
Proton-gated cation channels--neuronal acid sensors in the central and peripheral nervous system.
2001,
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
Wemmie,
The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
2002,
Pubmed
Wemmie,
Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning.
2003,
Pubmed
Wemmie,
Acid-sensing ion channels: advances, questions and therapeutic opportunities.
2006,
Pubmed
Weng,
Cell type-specific expression of acid-sensing ion channels in hippocampal interneurons.
2010,
Pubmed
Wong,
Blocking acid-sensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasome system-dependent mechanism.
2008,
Pubmed
Wu,
Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord.
2004,
Pubmed
Xiong,
Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.
2004,
Pubmed
Xiong,
Ca2+ -permeable acid-sensing ion channels and ischemic brain injury.
2006,
Pubmed
Xiong,
Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases.
2008,
Pubmed
Xu,
Calcium-permeable acid-sensing ion channel in nociceptive plasticity: a new target for pain control.
2009,
Pubmed
Yermolaieva,
Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a.
2004,
Pubmed
Zha,
Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects the density of dendritic spines.
2006,
Pubmed
Zha,
ASIC2 subunits target acid-sensing ion channels to the synapse via an association with PSD-95.
2009,
Pubmed
Ziemann,
The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behavior.
2009,
Pubmed
Ziemann,
Seizure termination by acidosis depends on ASIC1a.
2008,
Pubmed
