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J Neurosci
2011 Jun 29;3126:9723-34. doi: 10.1523/JNEUROSCI.1665-11.2011.
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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.
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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,
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 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 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 Bernardinelli,
Association between the ACCN1 gene and multiple sclerosis in Central East Sardinia.
2007,
Pubmed 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,
Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in depression-related behavior.
2009,
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 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,
Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death.
2005,
Pubmed Gao,
Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons.
2004,
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,
The mammalian sodium channel BNC1 is required for normal touch sensation.
2000,
Pubmed Price,
Cloning and expression of a novel human brain Na+ channel.
1996,
Pubmed
,
Xenbase 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,
H(+)-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels.
1998,
Pubmed Waldmann,
A proton-gated cation channel involved in acid-sensing.
1997,
Pubmed
,
Xenbase Waldmann,
Proton-gated cation channels--neuronal acid sensors in the central and peripheral nervous system.
2001,
Pubmed Wemmie,
The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
2002,
Pubmed Wemmie,
Acid-sensing ion channels: advances, questions and therapeutic opportunities.
2006,
Pubmed Wemmie,
Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning.
2003,
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,
Ca2+ -permeable acid-sensing ion channels and ischemic brain injury.
2006,
Pubmed Xiong,
Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.
2004,
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
