Gene Symbol: Asic2
Description: acid-sensing (proton-gated) ion channel 2
Alias: ACIC2, Accn1, BNC1, BNaC1, BNaC1a, Mdeg, acid-sensing ion channel 2, amiloride-sensitive brain sodium channel, amiloride-sensitive cation channel 1, neuronal (degenerin), brain sodium channel 1, degenerin
Species: mouse
Products:     Asic2

Top Publications

  1. Zha X, Costa V, Harding A, Reznikov L, Benson C, Welsh M. ASIC2 subunits target acid-sensing ion channels to the synapse via an association with PSD-95. J Neurosci. 2009;29:8438-46 pubmed publisher
    ..Although ASIC2 subunits are widely expressed in brain and modulate ASIC1a current, their function remains poorly understood...
  2. Duggan A, Garcia Anoveros J, Corey D. 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. J Biol Chem. 2002;277:5203-8 pubmed
    ..These ion channels are also expressed in the CNS. We identified the PDZ domain protein PICK1 as an interactor of BNaC1(ASIC2) in a yeast two-hybrid screen...
  3. Hattori T, Chen J, Harding A, Price M, Lu Y, Abboud F, et al. ASIC2a and ASIC3 heteromultimerize to form pH-sensitive channels in mouse cardiac dorsal root ganglia neurons. Circ Res. 2009;105:279-86 pubmed publisher
    ..currents from ASIC3(-/-) cardiac afferents matched the properties of ASIC2a channels, and currents from ASIC2(-/-) cardiac afferents matched the properties of ASIC3 channels...
  4. Jiang Q, Li M, Papasian C, Branigan D, Xiong Z, Wang J, et al. Characterization of acid-sensing ion channels in medium spiny neurons of mouse striatum. Neuroscience. 2009;162:55-66 pubmed publisher
    ..ASIC currents were diminished in MSNs from ASIC1, but not ASIC2, null mice. Furthermore, a drop in pH induced calcium influx by activating homomeric ASIC1a channels...
  5. Drew L, Rohrer D, Price M, Blaver K, Cockayne D, Cesare P, et al. Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones. J Physiol. 2004;556:691-710 pubmed
    ..transducer molecules are members of the acid-sensing ion channel (ASIC) family; nerve fibre recordings have shown ASIC2 and ASIC3 null mutants have aberrant responses to suprathreshold mechanical stimuli...
  6. Page A, Brierley S, Martin C, Hughes P, Blackshaw L. Acid sensing ion channels 2 and 3 are required for inhibition of visceral nociceptors by benzamil. Pain. 2007;133:150-60 pubmed
    ..Inhibition of colonic afferent mechanosensitivity by benzamil was markedly diminished in ASIC2-/- and ASIC3-/- mice, but unchanged in ASIC1a-/-...
  7. Jiang Q, Wang C, Fibuch E, Wang J, Chu X. Differential regulation of locomotor activity to acute and chronic cocaine administration by acid-sensing ion channel 1a and 2 in adult mice. Neuroscience. 2013;246:170-8 pubmed publisher
    Acid-sensing ion channels (ASICs) are densely expressed in the brain with ASIC1a and ASIC2 channels being the predominant subtypes...
  8. Gautam M, Benson C. Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits. FASEB J. 2013;27:793-802 pubmed publisher
    ..Currents from ASIC1a(-/-) muscle afferents were less pH-sensitive and displayed faster recovery, currents from ASIC2(-/-) mice showed diminished potentiation by zinc, and currents from ASIC3(-/-) mice displayed slower ..
  9. Lu Y, Ma X, Sabharwal R, Snitsarev V, Morgan D, Rahmouni K, et al. The ion channel ASIC2 is required for baroreceptor and autonomic control of the circulation. Neuron. 2009;64:885-97 pubmed publisher
    ..We found that aortic baroreceptor neurons in the nodose ganglia and their terminals express ASIC2. Conscious ASIC2 null mice developed hypertension, had exaggerated sympathetic and depressed parasympathetic ..

More Information


  1. Price M, Thompson R, Eshcol J, Wemmie J, Benson C. Stomatin modulates gating of acid-sensing ion channels. J Biol Chem. 2004;279:53886-91 pubmed
    Acid-sensing ion channels (ASICs) are H(+)-gated members of the degenerin/epithelial Na(+) channel (DEG/ENaC) family in vertebrate neurons...
  2. Roza C, Puel J, Kress M, Baron A, Diochot S, Lazdunski M, et al. Knockout of the ASIC2 channel in mice does not impair cutaneous mechanosensation, visceral mechanonociception and hearing. J Physiol. 2004;558:659-69 pubmed
    ..Mammalian degenerin homologues, the H(+)-gated ASIC channels, are expressed in sensory neurones and are therefore interesting ..
  3. Askwith C, Wemmie J, Price M, Rokhlina T, Welsh M. Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons. J Biol Chem. 2004;279:18296-305 pubmed
    Hippocampal neurons express subunits of the acid-sensing ion channel (ASIC1 and ASIC2) and exhibit large cation currents that are transiently activated by acidic extracellular solutions...
  4. Benson C, Xie J, Wemmie J, Price M, Henss J, Welsh M, et al. Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons. Proc Natl Acad Sci U S A. 2002;99:2338-43 pubmed
    ..The biophysical properties of three degenerin/epithelial sodium (DEG/ENaC) channel subunits (BNC1, ASIC, and DRASIC), and their expression in DRG, suggest ..
  5. Sluka K, Price M, Breese N, Stucky C, Wemmie J, Welsh M. Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain. 2003;106:229-39 pubmed
    ..Therefore, interfering with ASIC3 might be of benefit in treatment or prevention of chronic hyperalgesia. ..
  6. Chu X, Wemmie J, Wang W, Zhu X, Saugstad J, Price M, et al. Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels. J Neurosci. 2004;24:8678-89 pubmed
    ..Our studies suggest that Zn2+ may play an important role in a negative feedback system for preventing overexcitation of neurons during normal synaptic transmission and ASIC1a-mediated excitotoxicity in pathological conditions. ..
  7. Cho J, Askwith C. Presynaptic release probability is increased in hippocampal neurons from ASIC1 knockout mice. J Neurophysiol. 2008;99:426-41 pubmed
    ..Together, these findings demonstrate that neurons from ASIC1 knockout mice have an increased probability of neurotransmitter release and indicate that ASIC1a can affect presynaptic mechanisms of synaptic transmission. ..
  8. Wemmie J, Chen J, Askwith C, Hruska Hageman A, Price M, Nolan B, et al. The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory. Neuron. 2002;34:463-77 pubmed
    ..These results identify ASIC as a key component of acid-activated currents and implicate these currents in processes underlying synaptic plasticity, learning, and memory. ..
  9. Price M, Lewin G, McIlwrath S, Cheng C, Xie J, Heppenstall P, et al. The mammalian sodium channel BNC1 is required for normal touch sensation. Nature. 2000;407:1007-11 pubmed
    ..However, the similarity of the brain sodium channel 1 (BNC1) to nematode proteins involved in mechanotransduction indicated that it might be a part of such a ..
  10. Page A, Brierley S, Martin C, Price M, Symonds E, Butler R, et al. Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function. Gut. 2005;54:1408-15 pubmed
    ..Here they investigate further ASIC1a in gut mechanoreceptors, and compare its influence with ASIC2 and ASIC3...
  11. Tong J, Wu W, Kong X, Wu P, Tian L, Du W, et al. Acid-sensing ion channels contribute to the effect of acidosis on the function of dendritic cells. J Immunol. 2011;186:3686-92 pubmed publisher
    As an H(+)-gated subgroup of the degenerin/epithelial Na(+) channel family, acid-sensing ion channels (ASICs) were reported to be involved in various physiological and pathological processes in neurons...
  12. Baron A, Voilley N, Lazdunski M, Lingueglia E. Acid sensing ion channels in dorsal spinal cord neurons. J Neurosci. 2008;28:1498-508 pubmed publisher
  13. Garcia Anoveros J, Derfler B, Neville Golden J, Hyman B, Corey D. BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels. Proc Natl Acad Sci U S A. 1997;94:1459-64 pubmed
    ..We have identified two new members of this superfamily (BNaC1 and BNaC2) in a human brain cDNA library...
  14. Wu J, Leng T, Jing L, Jiang N, Chen D, Hu Y, et al. Two di-leucine motifs regulate trafficking and function of mouse ASIC2a. Mol Brain. 2016;9:9 pubmed publisher
    ..In addition, mutating the second LL motif increased pH sensitivity of the channel. These data identify the LL motifs as a negative regulator of ASIC2a trafficking and function, and suggest novel regulatory mechanisms in acid signaling. ..
  15. Wultsch T, Painsipp E, Shahbazian A, Mitrovic M, Edelsbrunner M, Lazdunski M, et al. Deletion of the acid-sensing ion channel ASIC3 prevents gastritis-induced acid hyperresponsiveness of the stomach-brainstem axis. Pain. 2008;134:245-53 pubmed
    ..Since the acid-sensing ion channels ASIC2 and ASIC3 are expressed by primary afferent neurons, we examined whether knockout of the ASIC2 or ASIC3 gene ..
  16. Chen X, Whissell P, Orser B, MacDonald J. Functional modifications of acid-sensing ion channels by ligand-gated chloride channels. PLoS ONE. 2011;6:e21970 pubmed publisher
    ..We conclude that GABA(A) receptors and glycine receptors modify ASICs in neurons through mechanisms that require the opening of chloride channels. ..
  17. Santos Torres J, Slimak M, Auer S, Ibanez Tallon I. Cross-reactivity of acid-sensing ion channel and Na?-H? exchanger antagonists with nicotinic acetylcholine receptors. J Physiol. 2011;589:5109-23 pubmed publisher
    ..antagonists, amiloride and its analogues, suppressed nicotine-evoked responses in MHb neurones of wild-type and ASIC2 null mice, excluding a possible involvement of ASIC2 in the nAChR inhibition by amiloride...
  18. Jing L, Jiang Y, Jiang Q, Wang B, Chu X, Zha X. The interaction between the first transmembrane domain and the thumb of ASIC1a is critical for its N-glycosylation and trafficking. PLoS ONE. 2011;6:e26909 pubmed publisher
    ..These results suggest that correct folding of extracellular ectodomain plays a critical role in ASIC1a biogenesis and function. ..
  19. Cohen Tannoudji M, Vandormael Pournin S, Le Bras S, Coumailleau F, Babinet C, Baldacci P. A 2-Mb YAC/BAC-based physical map of the ovum mutant (Om) locus region on mouse chromosome 11. Genomics. 2000;68:273-82 pubmed
    ..Two other genes (Rad51l3 and Schlafen 2) and one EST (D11Wsu78e) were also mapped in the Om region. This integrated map provides support for the identification of additional candidate genes for the DDK syndrome. ..
  20. Kusama N, Gautam M, Harding A, Snyder P, Benson C. Acid-sensing ion channels (ASICs) are differentially modulated by anions dependent on their subunit composition. Am J Physiol Cell Physiol. 2013;304:C89-101 pubmed publisher
    ..We speculate that modulation of ASIC gating by Cl(-) is a novel mechanism to sense shifts in extracellular fluid composition. ..
  21. Hughes P, Brierley S, Young R, Blackshaw L. Localization and comparative analysis of acid-sensing ion channel (ASIC1, 2, and 3) mRNA expression in mouse colonic sensory neurons within thoracolumbar dorsal root ganglia. J Comp Neurol. 2007;500:863-75 pubmed
    ..QPCR of whole thoracolumbar DRG revealed and abundance of ASIC2 > ASIC1 > ASIC3...
  22. Du J, Reznikov L, Price M, Zha X, Lu Y, Moninger T, et al. Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala. Proc Natl Acad Sci U S A. 2014;111:8961-6 pubmed publisher
    ..They also indicate that protons and ASICs are a neurotransmitter/receptor pair critical for amygdala-dependent learning and memory. ..
  23. Peng B, Ahmad S, Chen S, Chen P, Price M, Lin X. 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. J Neurosci. 2004;24:10167-75 pubmed
    Ion channels in the degenerin-epithelial sodium channel (DEG-ENaC) family perform diverse functions, including mechanosensation...
  24. Lin S, Cheng Y, Banks R, Min M, Bewick G, Chen C. Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors. Nat Commun. 2016;7:11460 pubmed publisher
    ..We conclude that, at least in mouse, ASIC3 is a molecular determinant contributing to dynamic mechanosensitivity in proprioceptors. ..
  25. Ugawa S, Inagaki A, Yamamura H, Ueda T, Ishida Y, Kajita K, et al. Acid-sensing ion channel-1b in the stereocilia of mammalian cochlear hair cells. Neuroreport. 2006;17:1235-9 pubmed
    ..Our findings provide a novel molecular key to the understanding of cochlear physiology and pathophysiology. ..
  26. Price M, Gong H, Parsons M, Kundert J, Reznikov L, Bernardinelli L, et al. Localization and behaviors in null mice suggest that ASIC1 and ASIC2 modulate responses to aversive stimuli. Genes Brain Behav. 2014;13:179-94 pubmed publisher
    ..Like ASIC1, ASIC2 subunits are expressed in the brain and multimerize with ASIC1 to influence acid-evoked currents and facilitate ..
  27. Boyd C, NARAY FEJES TOTH A. Gene regulation of ENaC subunits by serum- and glucocorticoid-inducible kinase-1. Am J Physiol Renal Physiol. 2005;288:F505-12 pubmed
    ..In summary, we report for the first time that SGK1 regulates transcription of ENaC subunits. We propose that the effect of SGK1 on ENaC transcription is mediated by the activation of unidentified transcription factors. ..
  28. Lingueglia E, De Weille J, Bassilana F, Heurteaux C, Sakai H, Waldmann R, et al. A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells. J Biol Chem. 1997;272:29778-83 pubmed
    MDEG1 is a cation channel expressed in brain that belongs to the degenerin/epithelial Na+ channel superfamily...
  29. Kreple C, Lu Y, Taugher R, Schwager Gutman A, Du J, Stump M, et al. Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity. Nat Neurosci. 2014;17:1083-91 pubmed publisher
    ..we identified a previously unknown postsynaptic current during neurotransmission that was mediated by ASIC1A and ASIC2 and thus well positioned to regulate synapse structure and function...
  30. Gannon K, McKey S, Stec D, Drummond H. Altered myogenic vasoconstriction and regulation of whole kidney blood flow in the ASIC2 knockout mouse. Am J Physiol Renal Physiol. 2015;308:F339-48 pubmed publisher
    Previous studies from our laboratory have suggested that degenerin proteins contribute to myogenic constriction, a mechanism of blood flow regulation and protection against pressure-dependent organ injury, in renal vessels...
  31. Krauson A, Carattino M. The Thumb Domain Mediates Acid-sensing Ion Channel Desensitization. J Biol Chem. 2016;291:11407-19 pubmed publisher
    ..We propose that the thumb domain moves upon continuous exposure to an acidic extracellular milieu, assisting with the closing of the pore during channel desensitization. ..
  32. Li M, Leng T, Feng X, Yang T, Simon R, Xiong Z. Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke. J Biol Chem. 2016;291:18370-83 pubmed publisher
    ..Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. ..
  33. Ettaiche M, Guy N, Hofman P, Lazdunski M, Waldmann R. Acid-sensing ion channel 2 is important for retinal function and protects against light-induced retinal degeneration. J Neurosci. 2004;24:1005-12 pubmed
    ..Inactivation of the ASIC2 gene in mice leads to an increase in the rod electroretinogram a- and b-waves and thus to an enhanced gain of ..
  34. Detweiler N, Vigil K, Resta T, Walker B, Jernigan N. Role of acid-sensing ion channels in hypoxia- and hypercapnia-induced ventilatory responses. PLoS ONE. 2018;13:e0192724 pubmed publisher
    ..Whole-body plethysmography was used to monitor ventilatory parameters in conscious, unrestrained ASIC1, ASIC2, or ASIC3 knockout (-/-) and wild-type (WT) mice at baseline, during isocapnic hypoxemia and during hypercapnia...
  35. Chai S, Li M, Lan J, Xiong Z, Saugstad J, Simon R. A kinase-anchoring protein 150 and calcineurin are involved in regulation of acid-sensing ion channels ASIC1a and ASIC2a. J Biol Chem. 2007;282:22668-77 pubmed
  36. McIlwrath S, Hu J, Anirudhan G, Shin J, Lewin G. The sensory mechanotransduction ion channel ASIC2 (acid sensitive ion channel 2) is regulated by neurotrophin availability. Neuroscience. 2005;131:499-511 pubmed
    ..Here we have investigated whether the ASIC2 sodium channel, recently shown by us to be necessary for normal SAM sensitivity, might be regulated by BDNF and ..
  37. Richter T, Dvoryanchikov G, Roper S, Chaudhari N. Acid-sensing ion channel-2 is not necessary for sour taste in mice. J Neurosci. 2004;24:4088-91 pubmed
    The acid-sensitive cation channel acid-sensing ion channel-2 (ASIC2) is widely believed to be a receptor for acid (sour) taste in mammals on the basis of its physiological properties and expression in rat taste bud cells...
  38. Zhang G, Mao L, Wang J, Chu X. Upregulation of acid-sensing ion channel 1 protein expression by chronic administration of cocaine in the mouse striatum in vivo. Neurosci Lett. 2009;459:119-22 pubmed publisher
    ..injection of cocaine (20mg/kg, once daily for 5 consecutive days; 14 days of withdrawal) increased ASIC1, but not ASIC2, protein levels in the striatum, including the dorsal (caudate putamen) and the ventral (nucleus accumbens) ..
  39. Harding A, Kusama N, Hattori T, Gautam M, Benson C. ASIC2 subunits facilitate expression at the cell surface and confer regulation by PSD-95. PLoS ONE. 2014;9:e93797 pubmed publisher
    ..b>ASIC2 subunits are widely expressed throughout the brain, where they heteromultimerize with their partnering subunit, ..
  40. Deval E, Salinas M, Baron A, Lingueglia E, Lazdunski M. ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1. J Biol Chem. 2004;279:19531-9 pubmed
    ..This regulation by PKC requires PICK-1 (protein interacting with C kinase), a PDZ domain-containing protein, which interacts with the ASIC2b C terminus. ..
  41. Gannon K, Vanlandingham L, Jernigan N, Grifoni S, Hamilton G, Drummond H. Impaired pressure-induced constriction in mouse middle cerebral arteries of ASIC2 knockout mice. Am J Physiol Heart Circ Physiol. 2008;294:H1793-803 pubmed publisher
    ..ENaC proteins are closely related to acid-sensing ion channel 2 (ASIC2), a protein known to be required for normal mechanotransduction in certain sensory neurons...
  42. Wu J, Xu Y, Jiang Y, Xu J, Hu Y, Zha X. ASIC subunit ratio and differential surface trafficking in the brain. Mol Brain. 2016;9:4 pubmed publisher
    ..This finding provides important insights into the relative contribution of various ASIC complexes to acid signaling in neurons. ..
  43. Petroff E, Snitsarev V, Gong H, Abboud F. Acid sensing ion channels regulate neuronal excitability by inhibiting BK potassium channels. Biochem Biophys Res Commun. 2012;426:511-5 pubmed publisher
    ..Our data suggest that ASICs can act as endogenous pH-dependent inhibitors of BK channels, and thereby can reduce neuronal excitability. ..
  44. Everett E, Yin Z, Yan D, Zou F. Fine mapping of dental fluorosis quantitative trait loci in mice. Eur J Oral Sci. 2011;119 Suppl 1:8-12 pubmed publisher
    ..0 (31-45 cM or ? 22 Mb). Haplotype analysis between A/J and 129P3/J mice further reduced the QTL intervals. Accn1 was selected as a candidate gene based upon its location near the peak LOD score on Chr 11 and distant homology ..
  45. Moshourab R, Wetzel C, Martinez Salgado C, Lewin G. Stomatin-domain protein interactions with acid-sensing ion channels modulate nociceptor mechanosensitivity. J Physiol. 2013;591:5555-74 pubmed publisher
    ..Single gene deletion of asic3, asic2, stomatin, or stoml3 all result in deficits in the mechanosensitivity of distinct cutaneous afferents in the mouse...
  46. Staniland A, McMahon S. Mice lacking acid-sensing ion channels (ASIC) 1 or 2, but not ASIC3, show increased pain behaviour in the formalin test. Eur J Pain. 2009;13:554-63 pubmed publisher
    ..This was achieved by (1) direct comparison of the sensitivity of ASIC1, ASIC2, ASIC3 and TRPV1 knockout mice versus wildtype littermates to acute thermal and mechanical noxious stimuli and (2) ..
  47. Arteaga M, Coric T, Straub C, Canessa C. A brain-specific SGK1 splice isoform regulates expression of ASIC1 in neurons. Proc Natl Acad Sci U S A. 2008;105:4459-64 pubmed publisher
    ..Given that neurons express at least two splice isoforms, SGK1 and SGK1.1, driven by distinct promoters, any changes in SGK1 transcript level must be examined to define the isoform induced by each stimulus or neurological disorder. ..
  48. Jiang N, Wu J, Leng T, Yang T, Zhou Y, Jiang Q, et al. Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury. J Cereb Blood Flow Metab. 2017;37:528-540 pubmed publisher
    ..Current literature has focused on ASIC1a when studying acid signaling. The importance of ASIC2, which is also widely expressed in the brain, has not been appreciated...
  49. Garcia Anoveros J, Samad T, Zuvela Jelaska L, Woolf C, Corey D. Transport and localization of the DEG/ENaC ion channel BNaC1alpha to peripheral mechanosensory terminals of dorsal root ganglia neurons. J Neurosci. 2001;21:2678-86 pubmed
    ..Accordingly, BNaC1alpha channels might participate in the transduction of touch and painful mechanical stimuli. ..