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New Strategies in Stroke Intervention pp 153–173Cite as

Acid-Sensing Ion Channels (ASICs): New Targets in Stroke Treatment

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Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in peripheral sensory neurons and in neurons of the central nervous system. Recent studies have demonstrated that activation of these channels plays an important role in a variety of physiological and pathological processes such as nociception, mechanosensation, synaptic plasticity, and acidosis-mediated neuronal injury. In fact, significant drop of tissue pH or acidosis is a common feature of acute neurological conditions such as ischemic stroke, brain trauma, and epileptic seizures. This chapter provides an overview of the recent advance in electrophysiological, pharmacological characterization of ASICs, and their potential role in neurological diseases, with particular regard to stroke. Therapeutic potential of current available ASIC inhibitors is discussed.

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References

  1. Akopian AN, Chen CC, Ding Y, Cesare P, and Wood JN. A new member of the acid-sensing ion channel family. Neuroreport 11: 2217–2222, 2000.

    Article  PubMed  CAS  Google Scholar 

  2. Allen NJ and Attwell D. Modulation of ASIC channels in rat cerebellar Purkinje neurons by ischaemia-related signals. J Physiol 543: 521–529, 2002.

    Article  PubMed  CAS  Google Scholar 

  3. Alvarez de la Rosa D, Canessa CM, Fyfe GK, and Zhang P. Structure and regulation of amiloride-sensitive sodium channels. Annu Rev Physiol 62: 573–594, 2000.

    Article  Google Scholar 

  4. Alvarez de la Rosa D, Krueger SR, Kolar A, Shao D, Fitzsimonds RM, and Canessa CM. Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system. J Physiol 546: 77–87, 2003.

    Article  Google Scholar 

  5. Annunziato L, Pignataro G, and Di Renzo GF. Pharmacology of brain Na+/Ca2+ exchanger: from molecular biology to therapeutic perspectives. Pharmacol Rev 56: 633–654, 2004.

    Article  PubMed  CAS  Google Scholar 

  6. Arias RL, Sung ML, Vasylyev D, Zhang MY, Albinson K, Kubek K, Kagan N, Beyer C, Lin Q, Dwyer JM, Zaleska MM, Bowlby MR, Dunlop J, and Monaghan M. Amiloride is neuroprotective in an MPTP model of Parkinson's disease. Neurobiol Dis 31: 334–341, 2008.

    Article  PubMed  CAS  Google Scholar 

  7. Askwith CC, Wemmie JA, Price MP, Rokhlina T, and Welsh MJ. Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons. J Biol Chem 279: 18296–18305, 2004.

    Article  PubMed  CAS  Google Scholar 

  8. Bano D, Young KW, Guerin CJ, Lefeuvre R, Rothwell NJ, Naldini L, Rizzuto R, Carafoli E, and Nicotera P. Cleavage of the plasma membrane Na+/Ca2+ exchanger in excitotoxicity. Cell 120: 275–285, 2005.

    Article  PubMed  CAS  Google Scholar 

  9. Baron A, Deval E, Salinas M, Lingueglia E, Voilley N, and Lazdunski M. Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1. J Biol Chem 277: 50463–50468, 2002.

    Article  PubMed  CAS  Google Scholar 

  10. Baron A, Waldmann R, and Lazdunski M. ASIC-like, proton-activated currents in rat hippocampal neurons. J Physiol 539: 485–494, 2002.

    Article  PubMed  CAS  Google Scholar 

  11. Bassilana F, Champigny G, Waldmann R, de Weille JR, Heurteaux C, and Lazdunski M. The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties. J Biol Chem 272: 28819–28822, 1997.

    Article  PubMed  CAS  Google Scholar 

  12. Bassler EL, Ngo-Anh TJ, Geisler HS, Ruppersberg JP, and Grunder S. Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b. J Biol Chem 276: 33782–33787, 2001.

    Article  PubMed  CAS  Google Scholar 

  13. Benson CJ, Eckert SP, and McCleskey EW. Acid-evoked currents in cardiac sensory neurons: A possible mediator of myocardial ischemic sensation. Circ Res 84: 921–928, 1999.

    PubMed  CAS  Google Scholar 

  14. Benson CJ, Xie J, Wemmie JA, Price MP, Henss JM, Welsh MJ, and Snyder PM. Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons. Proc Natl Acad Sci USA 99: 2338–2343, 2002.

    Article  PubMed  CAS  Google Scholar 

  15. Benveniste M and Dingledine R. Limiting stroke-induced damage by targeting an acid channel. N Engl J Med 352: 85–86, 2005.

    Article  PubMed  CAS  Google Scholar 

  16. Cadiou H, Studer M, Jones NG, Smith ES, Ballard A, McMahon SB, and McNaughton PA. Modulation of acid-sensing ion channel activity by nitric oxide. J Neurosci 27: 13251–13260, 2007.

    Article  PubMed  CAS  Google Scholar 

  17. Canessa CM, Schild L, Buell G, Thorens B, Gautschi I, Horisberger JD, and Rossier BC. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature 367: 463–467, 1994.

    Article  PubMed  CAS  Google Scholar 

  18. Chai S, Li M, Lan J, Xiong ZG, Saugstad JA, and Simon RP. A kinase-anchoring protein 150 and calcineurin are involved in regulation of acid-sensing ion channels ASIC1a and ASIC2a. J Biol Chem 282: 22668–22677, 2007.

    Article  PubMed  CAS  Google Scholar 

  19. Champigny G, Voilley N, Waldmann R, and Lazdunski M. Mutations causing neurodegeneration in Caenorhabditis elegans drastically alter the pH sensitivity and inactivation of the mammalian H+-gated Na+ channel MDEG1. J Biol Chem 273: 15418–15422, 1998.

    Article  PubMed  CAS  Google Scholar 

  20. Chang SYLM, Li TF, Chu XP, Lan JQ, Thomson S, Jessick V, Meller R, Simon RP, and Xiong ZG. Involvement of acid-sensing ion channels in the generation of epileptic seizure activity. Society for Neuroscience. San Diego, Ca: 2007.

    Google Scholar 

  21. Chen CC, England S, Akopian AN, and Wood JN. A sensory neuron-specific, proton-gated ion channel. Proc Natl Acad Sci USA 95: 10240–10245, 1998.

    Article  PubMed  CAS  Google Scholar 

  22. Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, and Zimmer A. A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc Natl Acad Sci USA 99: 8992–8997, 2002.

    PubMed  CAS  Google Scholar 

  23. Chen X, Kalbacher H, and Grunder S. The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity. J Gen Physiol 126: 71–79, 2005.

    Article  PubMed  CAS  Google Scholar 

  24. Chesler M. The regulation and modulation of pH in the nervous system. Prog Neurobiol 34: 401–427, 1990.

    Article  PubMed  CAS  Google Scholar 

  25. Chesler M and Kaila K. Modulation of pH by neuronal activity. Trends Neurosci 15: 396–402, 1992.

    Article  PubMed  CAS  Google Scholar 

  26. Coghlan VM, Perrino BA, Howard M, Langeberg LK, Hicks JB, Gallatin WM, and Scott JD. Association of protein kinase A and protein phosphatase 2B with a common anchoring protein. Science 267: 108–111, 1995.

    Article  PubMed  CAS  Google Scholar 

  27. Colledge M, Dean RA, Scott GK, Langeberg LK, Huganir RL, and Scott JD. Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex. Neuron 27: 107–119, 2000.

    Article  PubMed  CAS  Google Scholar 

  28. Coryell MW, Ziemann AE, Westmoreland PJ, Haenfler JM, Kurjakovic Z, Zha XM, Price M, Schnizler MK, and Wemmie JA. Targeting ASIC1a reduces innate fear and alters neuronal activity in the fear circuit. Biol Psychiatry 62: 1140–1148, 2007.

    Article  PubMed  CAS  Google Scholar 

  29. Diochot S, Baron A, Rash LD, Deval E, Escoubas P, Scarzello S, Salinas M, and Lazdunski M. A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. Embo J 23: 1516–1525, 2004.

    Article  PubMed  CAS  Google Scholar 

  30. Dorofeeva NA, Barygin OI, Staruschenko A, Bolshakov KV, and Magazanik LG. Mechanisms of non-steroid anti-inflammatory drugs action on ASICs expressed in hippocampal interneurons. J Neurochem 106: 429–441, 2008.

    Article  PubMed  CAS  Google Scholar 

  31. Dube GR, Lehto SG, Breese NM, Baker SJ, Wang X, Matulenko MA, Honore P, Stewart AO, Moreland RB, and Brioni JD. Electrophysiological and in vivo characterization of A-317567, a novel blocker of acid sensing ion channels. Pain 117: 88–96, 2005.

    Article  PubMed  CAS  Google Scholar 

  32. Duggan A, Garcia-Anoveros J, and Corey DP. 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 277: 5203–5208, 2002.

    Article  PubMed  CAS  Google Scholar 

  33. Ekholm A, Kristian T, and Siesjo BK. Influence of hyperglycemia and of hypercapnia on cellular calcium transients during reversible brain ischemia. Exp Brain Res 104: 462–466, 1995.

    Article  PubMed  CAS  Google Scholar 

  34. Escoubas P, De Weille JR, Lecoq A, Diochot S, Waldmann R, Champigny G, Moinier D, Menez A, and Lazdunski M. Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels. J Biol Chem 275: 25116–25121, 2000.

    Article  PubMed  CAS  Google Scholar 

  35. Eskandari S, Snyder PM, Kreman M, Zampighi GA, Welsh MJ, and Wright EM. Number of subunits comprising the epithelial sodium channel. J Biol Chem 274: 27281–27286, 1999.

    Article  PubMed  CAS  Google Scholar 

  36. Ettaiche M, Deval E, Cougnon M, Lazdunski M, and Voilley N. Silencing acid-sensing ion channel 1a alters cone-mediated retinal function. J Neurosci 26: 5800–5809, 2006.

    Article  PubMed  CAS  Google Scholar 

  37. Faux MC and Scott JD. Regulation of the AKAP79-protein kinase C interaction by Ca2+/Calmodulin. J Biol Chem 272: 17038–17044, 1997.

    Article  PubMed  CAS  Google Scholar 

  38. Firsov D, Gautschi I, Merillat AM, Rossier BC, and Schild L. The heterotetrameric architecture of the epithelial sodium channel (ENaC). Embo J 17: 344–352, 1998.

    Article  PubMed  CAS  Google Scholar 

  39. Friese MA, Craner MJ, Etzensperger R, Vergo S, Wemmie JA, Welsh MJ, Vincent A, and Fugger L. Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system. Nat Med 13: 1483–1489, 2007.

    Article  PubMed  CAS  Google Scholar 

  40. Gao J, Duan B, Wang DG, Deng XH, Zhang GY, Xu L, and Xu TL. Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death. Neuron 48: 635–646, 2005.

    Article  PubMed  CAS  Google Scholar 

  41. Garcia-Anoveros J, Derfler B, Neville-Golden J, Hyman BT, and Corey DP. BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels. Proc Natl Acad Sci USA 94: 1459–1464, 1997.

    Article  PubMed  CAS  Google Scholar 

  42. Glantz SB, Amat JA, and Rubin CS. cAMP signaling in neurons: patterns of neuronal expression and intracellular localization for a novel protein, AKAP 150, that anchors the regulatory subunit of cAMP-dependent protein kinase II beta. Mol Biol Cell 3: 1215–1228, 1992.

    PubMed  CAS  Google Scholar 

  43. Grunder S, Geissler HS, Bassler EL, and Ruppersberg JP. A new member of acid-sensing ion channels from pituitary gland. Neuroreport 11: 1607–1611, 2000.

    Article  PubMed  CAS  Google Scholar 

  44. Hansen AJ and Zeuthen T. Extracellular ion concentrations during spreading depression and ischemia in the rat brain cortex. Acta Physiol Scand 113: 437–445, 1981.

    Article  PubMed  CAS  Google Scholar 

  45. Helmlinger G, Yuan F, Dellian M, and Jain RK. Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med 3: 177–182, 1997.

    Article  PubMed  CAS  Google Scholar 

  46. Hruska-Hageman AM, Wemmie JA, Price MP, and Welsh MJ. 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). Biochem J 361: 443–450, 2002.

    Article  PubMed  CAS  Google Scholar 

  47. Jasti J, Furukawa H, Gonzales EB, and Gouaux E. Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH. Nature 449: 316–323, 2007.

    Article  PubMed  CAS  Google Scholar 

  48. Klauck TM, Faux MC, Labudda K, Langeberg LK, Jaken S, and Scott JD. Coordination of three signaling enzymes by AKAP79, a mammalian scaffold protein. Science 271: 1589–1592, 1996.

    Article  PubMed  CAS  Google Scholar 

  49. Kleyman TR and Cragoe EJ Jr.. Amiloride and its analogs as tools in the study of ion transport. J Membr Biol 105: 1–21, 1988.

    Article  PubMed  CAS  Google Scholar 

  50. Krishtal O. The ASICs: signaling molecules? Modulators? Trends Neurosci 26: 477–483, 2003.

    Article  PubMed  CAS  Google Scholar 

  51. Leonard AS, Yermolaieva O, Hruska-Hageman A, Askwith CC, Price MP, Wemmie JA, and Welsh MJ. cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1. Proc Natl Acad Sci USA 100: 2029–2034, 2003.

    Article  PubMed  CAS  Google Scholar 

  52. Lilley S, LeTissier P, and Robbins J. The discovery and characterization of a proton-gated sodium current in rat retinal ganglion cells. J Neurosci 24: 1013–1022, 2004.

    Article  PubMed  CAS  Google Scholar 

  53. Lingueglia E, de Weille JR, Bassilana F, Heurteaux C, Sakai H, Waldmann R, and Lazdunski M. A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells. J Biol Chem 272: 29778–29783, 1997.

    Article  PubMed  CAS  Google Scholar 

  54. Miesenbock G, De Angelis DA, and Rothman JE. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394: 192–195, 1998.

    Article  PubMed  CAS  Google Scholar 

  55. Nedergaard M, Kraig RP, Tanabe J, and Pulsinelli WA. Dynamics of interstitial and intracellular pH in evolving brain infarct. Am J Physiol 260: R581–R588, 1991.

    PubMed  CAS  Google Scholar 

  56. Pignataro G, Gala R, Cuomo O, Tortiglione A, Giaccio L, Castaldo P, Sirabella R, Matrone C, Canitano A, Amoroso S, Di Renzo G, and Annunziato L. Two sodium/calcium exchanger gene products, NCX1 and NCX3, play a major role in the development of permanent focal cerebral ischemia. Stroke 35: 2566–2570, 2004.

    Article  PubMed  CAS  Google Scholar 

  57. Pignataro G, Simon RP, and Xiong ZG. Prolonged activation of ASIC1a and the time window for neuroprotection in cerebral ischaemia. Brain 130: 151–158, 2007.

    Article  PubMed  Google Scholar 

  58. Pignataro G, Tortiglione A, Scorziello A, Giaccio L, Secondo A, Severino B, Santagada V, Caliendo G, Amoroso S, Di Renzo G, and Annunziato L. Evidence for a protective role played by the Na+/Ca2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats. Neuropharmacology 46: 439–448, 2004.

    Article  PubMed  CAS  Google Scholar 

  59. Price MP, McIlwrath SL, Xie J, Cheng C, Qiao J, Tarr DE, Sluka KA, Brennan TJ, Lewin GR, and Welsh MJ. The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. Neuron 32: 1071–1083, 2001.

    Article  PubMed  CAS  Google Scholar 

  60. Price MP, Thompson RJ, Eshcol JO, Wemmie JA, and Benson CJ. Stomatin modulates gating of acid-sensing ion channels. J Biol Chem 279: 53886–53891, 2004.

    Article  PubMed  CAS  Google Scholar 

  61. Reeh PW and Steen KH. Tissue acidosis in nociception and pain. Prog Brain Res 113: 143–151, 1996.

    Article  PubMed  CAS  Google Scholar 

  62. Rehncrona S. Brain acidosis. Ann Emerg Med 14: 770–776, 1985.

    Article  PubMed  CAS  Google Scholar 

  63. Renard S, Lingueglia E, Voilley N, Lazdunski M, and Barbry P. Biochemical analysis of the membrane topology of the amiloride-sensitive Na+ channel. J Biol Chem 269: 12981–12986, 1994.

    PubMed  CAS  Google Scholar 

  64. Salinas M, Rash LD, Baron A, Lambeau G, Escoubas P, and Lazdunski M. The receptor site of the spider toxin PcTx1 on the proton-gated cation channel ASIC1a. J Physiol 570: 339–354, 2006.

    PubMed  CAS  Google Scholar 

  65. Saugstad JA, Roberts JA, Dong J, Zeitouni S, and Evans RJ. Analysis of the membrane topology of the acid-sensing ion channel 2a. J Biol Chem 279: 55514–55519, 2004.

    Article  PubMed  CAS  Google Scholar 

  66. Schild L, Schneeberger E, Gautschi I, and Firsov D. 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. J Gen Physiol 109: 15–26, 1997.

    Article  PubMed  CAS  Google Scholar 

  67. Siesjo BK, Katsura K, and Kristian T. Acidosis-related damage. Adv Neurol 71: 209–233, 1996.

    PubMed  CAS  Google Scholar 

  68. Sluka KA, Price MP, Breese NM, Stucky CL, Wemmie JA, and Welsh MJ. Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain 106: 229–239, 2003.

    Article  PubMed  CAS  Google Scholar 

  69. Smith ES, Cadiou H, and McNaughton PA. Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action. Neuroscience 145: 686–698, 2007.

    Article  PubMed  CAS  Google Scholar 

  70. Sutherland SP, Benson CJ, Adelman JP, and McCleskey EW. Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons. Proc Natl Acad Sci USA 98: 711–716, 2001.

    Article  PubMed  CAS  Google Scholar 

  71. Tombaugh GC and Sapolsky RM. Evolving concepts about the role of acidosis in ischemic neuropathology. J Neurochem 61: 793–803, 1993.

    Article  PubMed  CAS  Google Scholar 

  72. Voilley N, de Weille J, Mamet J, and Lazdunski M. Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci 21: 8026–8033, 2001.

    PubMed  CAS  Google Scholar 

  73. Vukicevic M and Kellenberger S. Modulatory effects of acid-sensing ion channels on action potential generation in hippocampal neurons. Am J Physiol Cell Physiol 287: C682–C690, 2004.

    Article  PubMed  CAS  Google Scholar 

  74. Waldmann R, Bassilana F, de Weille J, Champigny G, Heurteaux C, and Lazdunski M. Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons. J Biol Chem 272: 20975–20978, 1997.

    Article  PubMed  CAS  Google Scholar 

  75. Waldmann R, Champigny G, Bassilana F, Heurteaux C, and Lazdunski M. A proton-gated cation channel involved in acid-sensing. Nature 386: 173–177, 1997.

    Article  PubMed  CAS  Google Scholar 

  76. Waldmann R, Champigny G, Voilley N, Lauritzen I, and Lazdunski M. The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans. J Biol Chem 271: 10433–10436, 1996.

    Article  PubMed  CAS  Google Scholar 

  77. Wemmie JA, Askwith CC, Lamani E, Cassell MD, Freeman JH Jr., and Welsh MJ. Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning. J Neurosci 23: 5496–5502, 2003.

    PubMed  CAS  Google Scholar 

  78. Wemmie JA, Chen J, Askwith CC, Hruska-Hageman AM, Price MP, Nolan BC, Yoder PG, Lamani E, Hoshi T, Freeman JH Jr., and Welsh MJ. The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory. Neuron 34: 463–477, 2002.

    Article  PubMed  CAS  Google Scholar 

  79. Wemmie JA, Price MP, and Welsh MJ. Acid-sensing ion channels: advances, questions and therapeutic opportunities. Trends Neurosci 29: 578–586, 2006.

    Article  PubMed  CAS  Google Scholar 

  80. Wong HK, Bauer PO, Kurosawa M, Goswami A, Washizu C, Machida Y, Tosaki A, Yamada M, Knopfel T, Nakamura T, and Nukina N. Blocking acid-sensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasome system-dependent mechanism. Hum Mol Genet 17: 3223–3235, 2008.

    Article  PubMed  CAS  Google Scholar 

  81. Wu LJ, Duan B, Mei YD, Gao J, Chen JG, Zhuo M, Xu L, Wu M, and Xu TL. Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord. J Biol Chem 279: 43716–43724, 2004.

    Article  PubMed  CAS  Google Scholar 

  82. Xie J, Price MP, Wemmie JA, Askwith CC, and Welsh MJ. ASIC3 and ASIC1 mediate FMRFamide-related peptide enhancement of H+-gated currents in cultured dorsal root ganglion neurons. J Neurophysiol 89: 2459–2465, 2003.

    Article  PubMed  CAS  Google Scholar 

  83. Xiong ZG, Zhu XM, Chu XP, Minami M, Hey J, Wei WL, MacDonald JF, Wemmie JA, Price MP, Welsh MJ, and Simon RP. Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell 118: 687–698, 2004.

    Article  PubMed  CAS  Google Scholar 

  84. Xu TL and Xiong ZG. Dynamic regulation of acid-sensing ion channels by extracellular and intracellular modulators. Curr Med Chem 14: 1753–1763, 2007.

    Article  PubMed  CAS  Google Scholar 

  85. Yagi J, Wenk HN, Naves LA, and McCleskey EW. Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia. Circ Res 99: 501–509, 2006.

    Article  PubMed  CAS  Google Scholar 

  86. Yermolaieva O, Leonard AS, Schnizler MK, Abboud FM, and Welsh MJ. Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a. Proc Natl Acad Sci USA 101: 6752–6757, 2004.

    Article  PubMed  CAS  Google Scholar 

  87. Ziemann AE, Schnizler MK, Albert GW, Severson MA, Howard MA 3rd, Welsh MJ, and Wemmie JA. Seizure termination by acidosis depends on ASIC1a. Nat Neurosci 11: 816–822, 2008.

    Article  PubMed  CAS  Google Scholar 

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  1. Division Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy

    Giuseppe Pignataro

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    Lucio Annunziato

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Pignataro, G. (2009). Acid-Sensing Ion Channels (ASICs): New Targets in Stroke Treatment. In: Annunziato, L. (eds) New Strategies in Stroke Intervention. Contemporary Neuroscience. Humana Press. https://doi.org/10.1007/978-1-60761-280-3_9

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