Current perspectives on acid-sensing ion channels: New advances and therapeutic implications

Expert Review of Clinical Pharmacology

Volumn 3, Issue 3, 2010, Pages 331-346

  Nol, Jacques ^a   Salinas, Miguel ^a   Baron, Anne ^a   Diochot, Sylvie ^a   Deval, Emmanuel ^a   Lingueglia, Eric ^a  

^a INSTITUT DE PHARMACOLOGIE MOLÉCULAIRE ET CELLULAIRE   (France)

Author keywords

Acid sensing ion channel; Acidosis; Brain; Chemosensation; Dorsal root ganglia; Mechanosensation; Na+ channels; Neurons; Pain; Protons; Synapse

Indexed keywords

A 317567; ACID SENSING ION CHANNEL; ACID SENSING ION CHANNEL 1A; ACID SENSING ION CHANNEL 1B; ACID SENSING ION CHANNEL 2A; ACID SENSING ION CHANNEL 2B; ACID SENSING ION CHANNEL 3; ACID SENSING ION CHANNEL 4; AMIDINE; AMILORIDE; BENZAMIL; NEUROPEPTIDE; PSALMOTOXIN 1; SEA ANEMONE TOXIN; SPIDER VENOM; UNCLASSIFIED DRUG;

AMYGDALOID NUCLEUS; AUTISM; BRAIN ISCHEMIA; CELL PH; CHANNEL GATING; CHRONIC PAIN; DEPRESSION; FEAR; GENETIC ASSOCIATION; HIPPOCAMPUS; HUMAN; HUNTINGTON CHOREA; HYPERALGESIA; LEARNING; MECHANOTRANSDUCTION; MEMORY; MENTAL DEFICIENCY; MENTAL DISEASE; MULTIPLE SCLEROSIS; MYALGIA; NERVE CELL DEGENERATION; NERVE CELL PLASTICITY; NEUROMODULATION; NEUROPROTECTION; NOCICEPTION; NONHUMAN; PAIN; PARKINSON DISEASE; PHOTOTRANSDUCTION; POSTOPERATIVE PAIN; REVIEW; SEIZURE; SKIN PAIN; SPINAL GANGLION; SYNAPTIC TRANSMISSION; TRAUMATIC BRAIN INJURY; VISCERAL PAIN;

EID: 77952557109     PISSN: 17512433     EISSN: None     Source Type: Journal    
DOI: 10.1586/ecp.10.13     Document Type: Review

References (218)

1. + channel. J. Biol. Chem. 271 (14), 7879-7882 (1996).
2. Waldmann R, Champigny G, Voilley N, Lauritzen I, Lazdunski M. The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans. J. Biol. Chem. 271 (18), 10433-10436 (1996).
3. Garcia-Anoveros J, Derfler B, Neville-Golden J, Hyman BT, 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 (4), 1459-1464 (1997).
4. Krishtal OA, Pidoplichko VI. A receptor for protons in the nerve cell membrane. Neuroscience 5 (12), 2325-2327 (1980).
5. Gruol DL, Barker JL, Huang LY, MacDonald JF, Smith TG Jr. Hydrogen ions have multiple effects on the excitability of cultured mammalian neurons. Brain Res. 183 (1), 247-252 (1980).
6. Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M. A protongated cation channel involved in acidsensing. Nature 386 (6621), 173-177 (1997).
7. Kellenberger S, Schild L. Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure. Physiol. Rev. 82 (3), 735-767 (2002).
8. Canessa CM, Horisberger JD, Rossier BC. Epithelial sodium channel related to proteins involved in neurodegeneration. Nature 361 (6411), 467-470 (1993).
9. + channel. A new channel type with homologies to Caenorhabditis elegans degenerins. FEBS Lett. 318 (1), 95-99 (1993).
10. Driscoll M, Chalfie M. The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration. Nature 349 (6310), 588-593 (1991).
11. Huang M, Chalfie M. Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans. Nature 367 (6462), 467-470 (1994).
12. Liu J, Schrank B, Waterston RH. Interaction between a putative mechanosensory membrane channel and a collagen. Science 273 (5273), 361-364 (1996).
13. Syntichaki P, Tavernarakis N. Genetic models of mechanotransduction: the nematode Caenorhabditis elegans. Physiol. Rev. 84 (4), 1097-1153 (2004).
14. Lingueglia E, Champigny G, Lazdunski M, Barbry P. Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel. Nature 378 (6558), 730-733 (1995).
15. Lingueglia E, Deval E, Lazdunski M. FMRFamide-gated sodium channel and ASIC channels: a new class of ionotropic receptors for FMRFamide and related peptides. Peptides 27 (5), 1138-1152 (2006).
16. Chen CC, England S, Akopian AN, Wood JN. A sensory neuron-specific, proton-gated ion channel. Proc. Natl Acad. Sci. USA 95 (17), 10240-10245 (1998).
17. Bassler EL, Ngo-Anh TJ, Geisler HS, Ruppersberg JP, Grunder S. Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b. J. Biol. Chem. 276 (36), 33782-33787 (2001).
18. + channel MDEG1. J. Biol. Chem. 273 (25), 15418-15422 (1998).
19. Lingueglia E, de Weille JR, Bassilana F et al. A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells. J. Biol. Chem. 272 (47), 29778-29783 (1997).
20. Babinski K, Le K T, Seguela P. Molecular cloning and regional distribution of a human proton receptor subunit with biphasic functional properties. J. Neurochem. 72 (1), 51-57 (1999).
21. de Weille JR, Bassilana F, Lazdunski M, Waldmann R. Identification, functional expression and chromosomal localisation of a sustained human proton-gated cation channel. FEBS Lett. 433 (3), 257-260 (1998).
22. + channel specific for sensory neurons. J. Biol. Chem. 272, 20975-20978 (1997).
23. Ishibashi K, Marumo F. Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis. Biochem. Biophys. Res. Commun. 245 (2), 589-593 (1998).
24. Akopian AN, Chen CC, Ding Y, Cesare P, Wood JN. A new member of the acidsensing ion channel family. Neuroreport 11 (10), 2217-2222 (2000).
25. Grunder S, Geissler HS, Bassler EL, Ruppersberg JP. A new member of acid-sensing ion channels from pituitary gland. Neuroreport 11 (8), 1607-1611 (2000).
26. Duggan A, Garcia-Anoveros J, 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 (7), 5203-5208 (2002).
27. Hruska-Hageman AM, Wemmie JA, Price MP, 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 (Pt 3), 443-450 (2002).
28. Baron A, Deval E, Salinas M, Lingueglia E, Voilley N, Lazdunski M. Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1. J. Biol. Chem. 277 (52), 50463-50468 (2002).
29. Deval E, Salinas M, Baron A, Lingueglia E, Lazdunski M. ASIC2b-dependent regulation of ASIC3, an essential acidsensing ion channel subunit in sensory neurons via the partner protein PICK-1. J. Biol. Chem. 279 (19), 19531-19539 (2004).
30. Anzai N, Deval E, Schaefer L, Friend V, Lazdunski M, Lingueglia E. The multivalent PDZ domain-containing protein CIPP is a partner of acid-sensing ion channel 3 in sensory neurons. J. Biol. Chem. 277 (19), 16655-16661 (2002).
31. + exchanger regulatory factor-1. J. Biol. Chem. 281 (3), 1796-1807 (2006).
32. +- gated current. J. Biol. Chem. 279 (45), 46962-46968 (2004).
33. Zha XM, Costa V, Harding AM, Reznikov L, Benson CJ, Welsh MJ. ASIC2 subunits target acid-sensing ion channels to the synapse via an association with PSD-95. J. Neurosci. 29 (26), 8438-8446 (2009).
34. Schnizler MK, Schnizler K, Zha XM et al. The cytoskeletal protein alpha-actinin regulates acid-sensing ion channel 1a through a C-terminal interaction. J. Biol. Chem. 284 (5), 2697-2705 (2009).
35. Donier E, Rugiero F, Okuse K, Wood JN. Annexin II light chain p11 promotes functional expression of acid-sensing ion channel ASIC1a. J. Biol. Chem. 280 (46), 38666-38672 (2005).
36. Price MP, Thompson RJ, Eshcol JO, Wemmie JA, Benson CJ. Stomatin modulates gating of acid-sensing ion channels. J. Biol. Chem. 279 (51), 53886-53891 (2004).
37. Wetzel C, Hu J, Riethmacher D et al. A stomatin-domain protein essential for touch sensation in the mouse. Nature 445 (7124), 206-209 (2007).
38. Gao J, Duan B, Wang DG et al. Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death. Neuron 48 (4), 635-646 (2005).
39. Chai S, Li M, Lan J, Xiong ZG, Saugstad JA, Simon R P. A kinaseanchoring protein 150 and calcineurin are involved in regulation of acid-sensing ion channels ASIC1a and ASIC2a. J. Biol. Chem. 282 (31), 22668-22677 (2007).
40. Jasti J, Furukawa H, Gonzales EB, Gouaux E. Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH. Nature 449 (7160), 316-323 (2007).
41. Gonzales EB, Kawate T, Gouaux E. Pore architecture and ion sites in acidsensing ion channels and P2X receptors. Nature 460 (7255), 599-604 (2009).
42. Chen X, Grunder S. Permeating protons contribute to tachyphylaxis of Acid-Sensing Ion Channel (ASIC) 1a. J. Physiol. 579 (Pt 3), 657-670 (2007).
43. Sutherland SP, Benson CJ, Adelman JP, McCleskey EW. Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons. Proc. Natl Acad. Sci. USA 98 (2), 711-716 (2001).
44. Yermolaieva O, Leonard AS, Schnizler MK, Abboud FM, Welsh MJ. Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a. Proc. Natl Acad. Sci. USA 101 (17), 6752-6757 (2004).
45. 2+ entry. Cell Calcium 45 (4), 319-325 (2009).
46. Xiong ZG, Zhu XM, Chu XP et al. Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell 118 (6), 687-698 (2004).
47. 2+ influx in rat cortical neurons. J. Pharmacol. Exp. Ther. 327 (2), 491-502 (2008).
48. Zha XM, Wemmie JA, Green SH, Welsh MJ. Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects the density of dendritic spines. Proc. Natl Acad. Sci. USA 103 (44), 16556-16561 (2006).
49. Donier E, Rugiero F, Jacob C, Wood JN. Regulation of ASIC activity by ASIC4 - new insights into ASIC channel function revealed by a yeast two-hybrid assay. Eur. J. Neurosci. 28 (1), 74-86 (2008).
50. Baron A, Voilley N, Lazdunski M, Lingueglia E. Acid sensing ion channels in dorsal spinal cord neurons. J. Neurosci. 28 (6), 1498-1508 (2008).
51. Salinas M, Lazdunski M, Lingueglia E. Structural elements for the generation of sustained currents by the acid pain sensor ASIC3. J. Biol. Chem. 284 (46), 31851-31859 (2009).
52. Deval E, Baron A, Lingueglia E, Mazarguil H, Zajac JM, Lazdunski M. Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability. Neuropharmacology 44 (5), 662-671 (2003).
53. Yagi J, Wenk HN, Naves LA, McCleskey EW. Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia. Circ. Res. 99 (5), 501-509 (2006).
54. Deval E, Noel J, Lay N et al. ASIC3, a sensor of acidic and primary inflammatory pain. EMBO J. 27 (22), 3047-3055 (2008).
55. Li T, Yang Y, Canessa CM. Interaction of the aromatics Tyr-72/Trp-288 in the interface of the extracellular and transmembrane domains is essential for proton gating of acid-sensing ion channels. J. Biol. Chem. 284 (7), 4689-4694 (2009).
56. + gating of acid-sensing ion channel 1a. J. Biol. Chem. 283 (1), 572-581 (2008).
57. 2+ blocking site of acid-sensing ion channel (ASIC) 1: implications for channel gating. J. Gen. Physiol. 124 (4), 383-394 (2004).
58. Yang H, Yu Y, Li WG, Xu TL, Jiang H. Conformational sampling on acid-sensing ion channel 1 (ASIC1): implication for a symmetric conformation. Cell Res. 19 (8), 1035-1037 (2009).
59. Yang H, Yu Y, Li WG et al. Inherent dynamics of the acid-sensing ion channel 1 correlates with the gating mechanism. PLoS Biol. 7 (7), e1000151 (2009).
60. 2+ blockade. Neuron 37 (1), 75-84 (2003).
61. 2+ block vs. allosteric mechanism. J. Gen. Physiol. 127 (2), 109-117 (2006).
62. Sherwood T, Franke R, Conneely S, Joyner J, Arumugan P, Askwith C. Identification of protein domains that control proton and calcium sensitivity of ASIC1a. J. Biol. Chem. 284 (41), 27899-27907 (2009).
63. 2+) ions. Brain Res. 900 (2), 277-281 (2001).
64. Zhang P, Canessa CM. Single channel properties of rat acid-sensitive ion channel-1α, -2a, and -3 expressed in Xenopus oocytes. J. Gen. Physiol. 120 (4), 553-566 (2002).
65. Zhang P, Canessa CM. Single-channel properties of recombinant acid-sensitive ion channels formed by the subunits ASIC2 and ASIC3 from dorsal root ganglion neurons expressed in Xenopus oocytes. J. Gen. Physiol. 117 (6), 563-572 (2001).
66. Coscoy S, de Weille JR, Lingueglia E, Lazdunski M. The pre-transmembrane 1 domain of acid-sensing ion channels participates in the ion pore. J. Biol. Chem. 274 (15), 10129-10132 (1999).
67. Dube GR, Lehto SG, Breese NM et al. Electrophysiological and in vivo characterization of A-317567, a novel blocker of acid sensing ion channels. Pain 117 (1-2), 88-96 (2005).
68. Voilley N, de Weille J, Mamet J, Lazdunski M. Nonsteroid antiinflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J. Neurosci. 21 (20), 8026-8033 (2001).
69. Voilley N. Acid-sensing ion channels (ASICs): new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs). Curr. Drug Targets Inflamm. Allergy 3 (1), 71-79 (2004).
70. Ugawa S, Ishida Y, Ueda T, Inoue K, Nagao M, Shimada S. Nafamostat mesilate reversibly blocks acid-sensing ion channel currents. Biochem. Biophys. Res. Commun. 363 (1), 203-208 (2007).
71. Garza A, Lopez-Ramirez O, Vega R, Soto E. The aminoglycosides modulate the acid-sensing ionic-channel (ASIC) currents in dorsal-root ganglion neurons from the rat. J. Pharmacol. Exp. Ther. 332 (2), 489-499 (2009).
72. Chen X, Qiu L, Li M et al. Diarylamidines: High potency inhibitors of acid-sensing ion channels. Neuropharmacology doi: 10.1016/j.neuropharm.2010.01. 011 (2010) (Epub ahead of print).
73. Allen NJ, Attwell D. Modulation of ASIC channels in rat cerebellar Purkinje neurons by ischaemia-related signals. J. Physiol. 543 (Pt 2), 521-529 (2002).
74. Babinski K, Catarsi S, Biagini G, Seguela P. Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+. J. Biol. Chem. 275 (37), 28519-28525 (2000).
75. 2+) in cultured hypothalamic neurons of the rat. Neuroscience 145 (2), 631-641 (2007).
76. Staruschenko A, Dorofeeva NA, Bolshakov K V, Stockand JD. Subunitdependent cadmium and nickel inhibition of acid-sensing ion channels. Dev. Neurobiol. 67 (1), 97-107 (2007).
77. Wang W, Duan B, Xu H, Xu L, Xu TL. Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead. J. Biol. Chem. 281 (5), 2497-2505 (2006).
78. Chu XP, Wemmie JA, Wang WZ et al. Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels. J. Neurosci. 24 (40), 8678-8689 (2004).
79. + are coactivators of acid-sensing ion channels. J. Biol. Chem. 276 (38), 35361-35367 (2001).
80. Baron A, Waldmann R, Lazdunski M. ASIC-like, proton-activated currents in rat hippocampal neurons. J. Physiol. 539 (Pt 2), 485-494 (2002).
81. Diochot S, Salinas M, Baron A, Escoubas P, Lazdunski M. Peptides inhibitors of acid-sensing ion channels. Toxicon 49 (2), 271-284 (2007).
82. + channels. J. Biol. Chem. 275 (33), 25116-25121 (2000).
83. Salinas M, Rash LD, Baron A, Lambeau G, Escoubas P, Lazdunski M. The receptor site of the spider toxin PcTx1 on the protongated cation channel ASIC1a. J. Physiol. 570 (Pt 2), 339-354 (2006).
84. Escoubas P, Bernard C, Lambeau G, Lazdunski M, Darbon H. Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels. Protein Sci. 12 (7), 1332-1343 (2003).
85. Diochot S, Baron A, Rash LD et al. A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. EMBO J. 23 (7), 1516-1525 (2004).
86. Chagot B, Escoubas P, Diochot S, Bernard C, Lazdunski M, Darbon H. Solution structure of APETx2, a specific peptide inhibitor of ASIC3 proton-gated channels. Protein Sci. 14 (8), 2003-2010 (2005).
87. + affinity. J. Gen. Physiol. 126 (1), 71-79 (2005).
88. Qadri YJ, Berdiev BK, Song Y, Lippton HL, Fuller CM, Benos DJ. Psalmotoxin-1 docking to human acid-sensing ion channel-1. J. Biol. Chem. 284 (26), 17625-17633 (2009).
89. Chen X, Kalbacher H, Grunder S. Interaction of acid-sensing ion channel (ASIC) 1 with the tarantula toxin psalmotoxin 1 is state dependent. J. Gen. Physiol. 127 (3), 267-276 (2006).
90. Askwith CC, Cheng C, Ikuma M, Benson C, Price MP, Welsh MJ. Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels. Neuron 26 (1), 133-141 (2000).
91. Catarsi S, Babinski K, Seguela P. Selective modulation of heteromeric ASIC protongated channels by neuropeptide FF. Neuropharmacology 41 (5), 592-600 (2001).
92. Chen X, Paukert M, Kadurin I, Pusch M, Grunder S. Strong modulation by RFamide neuropeptides of the ASIC1b/3 heteromer in competition with extracellular calcium. Neuropharmacology 50 (8), 964-974 (2006).
93. +-gated currents in cultured dorsal root ganglion neurons. J. Neurophysiol. 89 (5), 2459-2465 (2003).
94. Sherwood TW, Askwith CC. Endogenous arginine-phenylalanine-amide-related peptides alter steady-state desensitization of ASIC1a. J. Biol. Chem. 283 (4), 1818-1830 (2008).
95. +-activated currents in hippocampal neurons. J. Biol. Chem. 279 (18), 18296-18305 (2004).
96. Ostrovskaya O, Moroz L, Krishtal O. Modulatory action of RFamide-related peptides on acid-sensing ionic channels is pH dependent: the role of arginine. J. Neurochem. 91 (1), 252-255 (2004).
97. Xie J, Price MP, Berger AL, Welsh MJ. DRASIC contributes to pH-gated currents in large dorsal root ganglion sensory neurons by forming heteromultimeric channels. J. Neurophysiol. 87 (6), 2835-2843 (2002).
98. Sherwood TW, Askwith CC. Dynorphin opioid peptides enhance acid-sensing ion channel 1a activity and acidosis-induced neuronal death. J. Neurosci. 29 (45), 14371-14380 (2009).
99. Wemmie JA, Askwith CC, Lamani E, Cassell MD, Freeman JH, Jr., Welsh MJ. Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning. J. Neurosci. 23 (13), 5496-5502 (2003).
100. Waldmann R, Lazdunski M. H+-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. Curr. Opin. Neurobiol. 8 (3), 418-424 (1998).
101. Wemmie JA, Chen J, Askwith CC et al. The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory. Neuron 34 (3), 463-477 (2002).
102. Alvarez de la Rosa D, Krueger SR, Kolar A, Shao D, Fitzsimonds RM, Canessa CM. Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system. J. Physiol. 546 (Pt 1), 77-87 (2003).
103. Roza C, Puel JL, Kress M et al. Knockout of the ASIC2 channel in mice does not impair cutaneous mechanosensation, visceral mechanonociception and hearing. J. Physiol. 558 (Pt 2), 659-669 (2004).
104. Cho JH, Askwith CC. Presynaptic release probability is increased in hippocampal neurons from ASIC1 knockout mice. J. Neurophysiol. 99 (2), 426-441 (2008).
105. Maren S. An acid-sensing channel sows fear and panic. Cell 139 (5), 867-869 (2009).
106. Coryell MW, Ziemann AE, Westmoreland PJ et al. Targeting ASIC1a reduces innate fear and alters neuronal activity in the fear circuit. Biol. Psychiatry 62 (10), 1140-1148 (2007).
107. Coryell MW, Wunsch AM, Haenfler JM et al. Restoring acid-sensing ion channel-1a in the amygdala of knock-out mice rescues fear memory but not unconditioned fear responses. J. Neurosci. 28 (51), 13738-13741 (2008).
108. Wemmie JA, Coryell MW, Askwith CC et al. Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior. Proc. Natl Acad. Sci. USA 101 (10), 3621-3626 (2004).
109. Ziemann AE, Allen JE, Dahdaleh NS et al. The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behavior. Cell 139 (5), 1012-1021 (2009).
110. Coryell MW, Wunsch AM, Haenfler JM et al. Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in depression-related behavior. J. Neurosci. 29 (17), 5381-5388 (2009).
111. Friese MA, Craner MJ, Etzensperger R et al. Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system. Nat. Med. 13 (12), 1483-1489 (2007).
112. Arias RL, Sung ML, Vasylyev D et al. Amiloride is neuroprotective in an MPTP model of Parkinson's disease. Neurobiol. Dis. 31 (3), 334-341 (2008).
113. Wong HK, Bauer PO, Kurosawa M et al. Blocking acid-sensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasome systemdependent mechanism. Hum. Mol. Genet. 17 (20), 3223-3235 (2008).
114. Zhao X, Gorin FA, Berman RF, Lyeth BG. Differential hippocampal protection when blocking intracellular sodium and calcium entry during traumatic brain injury in rats. J. Neurotrauma 25 (10), 1195-1205 (2008).
115. Ziemann AE, Schnizler MK, Albert GW et al. Seizure termination by acidosis depends on ASIC1a. Nat. Neurosci. 11 (7), 816-822 (2008).
116. Bolshakov K V, Essin K V, Buldakova SL et al. Characterization of acid-sensitive ion channels in freshly isolated rat brain neurons. Neuroscience 110 (4), 723-730 (2002).
117. Ali A, Pillai K P, Ahmad FJ, Dua Y, Vohora D. Anticonvulsant effect of amiloride in pentetrazole-induced status epilepticus in mice. Pharmacol. Rep. 58 (2), 242-245 (2006).
118. Luszczki JJ, Sawicka KM, Kozinska J, Dudra-Jastrzebska M, Czuczwar SJ. Amiloride enhances the anticonvulsant action of various antiepileptic drugs in the mouse maximal electroshock seizure model. J. Neural. Transm. 116 (1), 57-66 (2009).
119. N'Gouemo P. Amiloride delays the onset of pilocarpine-induced seizures in rats. Brain Res. 1222, 230-232 (2008).
120. Miesenbock G, De Angelis DA, Rothman JE. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394 (6689), 192-195 (1998).
121. 2+ current in mammalian cone photoreceptors. Neuron 32 (6), 1107-1117 (2001).
122. Barnes S, Merchant V, Mahmud F. Modulation of transmission gain by protons at the photoreceptor output synapse. Proc. Natl Acad. Sci. USA 90 (21), 10081-10085 (1993).
123. Krishtal O. The ASICs: signaling molecules? Modulators? Trends Neurosci. 26 (9), 477-483 (2003).
124. Beg AA, Ernstrom GG, Nix P, Davis MW, Jorgensen EM. Protons act as a transmitter for muscle contraction in C. elegans. Cell 132 (1), 149-160 (2008).
125. Garcia-Anoveros J, Samad TA, Zuvela-Jelaska L, Woolf CJ, Corey DP. Transport and localization of the DEG/ENaC ion channel BNaC1α to peripheral mechanosensory terminals of dorsal root ganglia neurons. J. Neurosci. 21 (8), 2678-2686 (2001).
126. Price MP, McIlwrath SL, Xie J et al. The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. Neuron 32 (6), 1071-1083 (2001).
127. Alvarez de la Rosa D, Zhang P, Shao D, White F, Canessa CM. Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. Proc. Natl Acad. Sci. USA 99 (4), 2326-2331 (2002).
128. Price MP, Lewin GR, McIlwrath SL et al. The mammalian sodium channel BNC1 is required for normal touch sensation. Nature 407 (6807), 1007-1011 (2000).
129. Molliver DC, Immke DC, Fierro L, Pare M, Rice FL, McCleskey EW. ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons. Mol. Pain 1 (1), 35 (2005).
130. Ugawa S, Ueda T, Yamamura H, Shimada S. In situ hybridization evidence for the coexistence of ASIC and TRPV1 within rat single sensory neurons. Brain Res. Mol. Brain Res. 136 (1-2), 125-133 (2005).
131. Olson TH, Riedl MS, Vulchanova L, Ortiz-Gonzalez XR, Elde R. An acid sensing ion channel (ASIC) localizes to small primary afferent neurons in rats. Neuroreport 9 (6), 1109-1113 (1998).
132. Duan B, Wu LJ, Yu YQ et al. Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity. J. Neurosci. 27 (41), 11139-11148 (2007).
133. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389 (6653), 816-824 (1997).
134. Yudin YK, Tamarova ZA, Ostrovskaya OI, Moroz LL, Krishtal OA. RFa-related peptides are algogenic: evidence in vitro and in vivo. Eur. J. Neurosci. 20 (5), 1419-1423 (2004).
135. Mamet J, Baron A, Lazdunski M, Voilley N. Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. J. Neurosci. 22 (24), 10662-10670 (2002).
136. Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, Zimmer A. A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc. Natl Acad. Sci. USA 99 (13), 8992-8997 (2002).
137. Page AJ, Brierley SM, Martin CM et al. The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function. Gastroenterology 127 (6), 1739-1747 (2004).
138. Mogil JS, Breese NM, Witty MF et al. Transgenic expression of a dominantnegative ASIC3 subunit leads to increased sensitivity to mechanical and inflammatory stimuli. J. Neurosci. 25 (43), 9893-9901 (2005).
139. Rocha-Gonzalez HI, Herrejon-Abreu EB, Lopez-Santillan FJ, Garcia-Lopez BE, Murbartian J, Granados-Soto V. Acid increases inflammatory pain in rats: effect of local peripheral ASICs inhibitors. Eur. J. Pharmacol. 603 (1-3), 56-61 (2009).
140. Yiangou Y, Facer P, Smith JA et al. Increased acid-sensing ion channel ASIC-3 in inflamed human intestine. Eur. J. Gastroenterol. Hepatol. 13 (8), 891-896 (2001).
141. Mamet J, Lazdunski M, Voilley N. How nerve growth factor drives physiological and inflammatory expressions of acidsensing ion channel 3 in sensory neurons. J. Biol. Chem. 278 (49), 48907-48913 (2003).
142. Smith ES, Cadiou H, McNaughton PA. Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action. Neuroscience 145 (2), 686-698 (2007).
143. Cadiou H, Studer M, Jones NG et al. Modulation of acid-sensing ion channel activity by nitric oxide. J. Neurosci. 27 (48), 13251-13260 (2007).
144. Steen KH, Issberner U, Reeh PW. Pain due to experimental acidosis in human skin: evidence for non-adapting nociceptor excitation. Neurosci. Lett. 199 (1), 29-32 (1995).
145. Ugawa S, Ueda T, Ishida Y, Nishigaki M, Shibata Y, Shimada S. Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors. J. Clin. Invest. 110 (8), 1185-1190 (2002).
146. Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB. Acidinduced pain and its modulation in humans. J. Neurosci. 24 (48), 10974-10979 (2004).
147. McMahon SB, Jones NG. Plasticity of pain signaling: role of neurotrophic factors exemplified by acid-induced pain. J. Neurobiol. 61 (1), 72-87 (2004).
148. Yen YT, Tu PH, Chen CJ, Lin Y W, Hsieh ST, Chen CC. Role of acid-sensing ion channel 3 in sub-acute-phase inflammation. Mol. Pain 5, 1 (2009).
149. Mazzuca M, Heurteaux C, Alloui A et al. A tarantula peptide against pain via ASIC1a channels and opioid mechanisms. Nat. Neurosci. 10 (8), 943-945 (2007).
150. Leffler A, Monter B, Koltzenburg M. The role of the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) in proton sensitivity of subpopulations of primary nociceptive neurons in rats and mice. Neuroscience 139 (2), 699-709 (2006).
151. Ikeuchi M, Kolker SJ, Sluka KA. Acidsensing ion channel 3 expression in mouse knee joint afferents and effects of carrageenan-induced arthritis. J. Pain 10 (3), 336-342 (2009).
152. Walder RY, Rasmussen LA, Rainier JD, Light AR, Wemmie JA, Sluka KA. ASIC1 and ASIC3 play different roles in the development of hyperalgesia after inflammatory muscle injury. J. Pain 11 (3), 210-218 (2009).
153. Sluka KA, Price MP, Breese NM, Stucky CL, Wemmie JA, Welsh MJ. Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain 106 (3), 229-239 (2003).
154. Sluka KA, Radhakrishnan R, Benson CJ et al. ASIC3 in muscle mediates mechanical, but not heat, hyperalgesia associated with muscle inflammation. Pain 129 (1-2), 102-112 (2007).
155. Ikeuchi M, Kolker SJ, Burnes LA, Walder RY, Sluka KA. Role of ASIC3 in the primary and secondary hyperalgesia produced by joint inflammation in mice. Pain 137 (3), 662-669 (2008).
156. -/- mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294 (4), R1347-R1355 (2008).
157. Benson CJ, Sutherland SP. Toward an understanding of the molecules that sense myocardial ischemia. Ann. NY Acad. Sci. 940, 96-109 (2001).
158. + channel on ischemia-sensing neurons. Nat. Neurosci. 4 (9), 869-870 (2001).
159. Sugiura T, Dang K, Lamb K, Bielefeldt K, Gebhart GF. Acid-sensing properties in rat gastric sensory neurons from normal and ulcerated stomach. J. Neurosci. 25 (10), 2617-2627 (2005).
160. Bielefeldt K, Davis BM. Differential effects of ASIC3 and TRPV1 deletion on gastroesophageal sensation in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 294 (1), G130-138 (2008).
161. Wultsch T, Painsipp E, Shahbazian A et al. Deletion of the acid-sensing ion channel ASIC3 prevents gastritis-induced acid hyperresponsiveness of the stomachbrainstem axis. Pain 134 (3), 245-253 (2008).
162. Holzer P. Taste receptors in the gastrointestinal tract. V. Acid sensing in the gastrointestinal tract. Am. J. Physiol. Gastrointest. Liver Physiol. 292 (3), G699-G705 (2007).
163. Page AJ, Brierley SM, Martin CM et al. Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function. Gut 54 (10), 1408-1415 (2005).
164. Hughes PA, Brierley SM, Young RL, Blackshaw LA. 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. 500 (5), 863-875 (2007).
165. Jones RC 3rd, Xu L, Gebhart GF. The mechanosensitivity of mouse colon afferent fibers and their sensitization by inflammatory mediators require transient receptor potential vanilloid 1 and acid-sensing ion channel 3. J. Neurosci. 25 (47), 10981-10989 (2005).
166. Jones RC, 3rd, Otsuka E, Wagstrom E, Jensen CS, Price MP, Gebhart GF. Short-term sensitization of colon mechanoreceptors is associated with long-term hypersensitivity to colon distention in the mouse. Gastroenterology 133 (1), 184-194 (2007).
167. Gu Q, Lee LY. Characterization of acid-signaling in rat vagal pulmonary sensory neurons. Am. J. Physiol. Lung Cell Mol. Physiol. 291 (1), L58-L65 (2006).
168. Fukuda T, Ichikawa H, Terayama R, Yamaai T, Kuboki T, Sugimoto T. ASIC3-immunoreactive neurons in the rat vagal and glossopharyngeal sensory ganglia. Brain Res. 1081 (1), 150-155 (2006).
169. Groth M, Helbig T, Grau V, Kummer W, Haberberger RV. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels. Respir. Res. 7, 96 (2006).
170. Faisy C, Planquette B, Naline E et al. Acid-induced modulation of airway basal tone and contractility: role of acid-sensing ion channels (ASICs) and TRPV1 receptor. Life Sci. 81 (13), 1094-1102 (2007).
171. Canning BJ, Farmer DG, Mori N. Mechanistic studies of acid evoked coughing in anesthetized guinea pigs. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291 (2), R454-R463 (2006).
172. Ricciardolo FL. Mechanisms of citric acid-induced bronchoconstriction. Am. J. Med. 111 (Suppl. 8 A), 18S-24S (2001).
173. Kollarik M, Undem BJ. Mechanisms of acid-induced activation of airway afferent nerve fibres in guinea-pig. J. Physiol. 543 (Pt 2), 591-600 (2002).
174. Wu LJ, Duan B, Mei YD et al. Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord. J. Biol. Chem. 279 (42), 43716-43724 (2004).
175. Kontinen VK, Aarnisalo AA, Idanpaan-Heikkila JJ, Panula P, Kalso E. Neuropeptide FF in the rat spinal cord during carrageenan inflammation. Peptides 18 (2), 287-292 (1997).
176. Yang HY, Iadarola MJ. Activation of spinal neuropeptide FF and the neuropeptide FF receptor 2 during inflammatory hyperalgesia in rats. Neuroscience 118 (1), 179-187 (2003).
177. Vilim FS, Aarnisalo AA, Nieminen ML et al. Gene for pain modulatory neuropeptide NPFF: induction in spinal cord by noxious stimuli. Mol. Pharmacol. 55 (5), 804-811 (1999).
178. Bounoutas A, Chalfie M. Touch sensitivity in Caenorhabditis elegans. Pflugers Arch. 454 (5), 691-702 (2007).
179. O'Hagan R, Chalfie M, Goodman MB. The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals. Nat. Neurosci. 8 (1), 43-50 (2005).
180. Suzuki H, Kerr R, Bianchi L et al. In vivo imaging of C. elegans mechanosensory neurons demonstrates a specific role for the MEC-4 channel in the process of gentle touch sensation. Neuron 39 (6), 1005-1017 (2003).
181. + channels. J. Biol. Chem. 277 (4), 2369-2372 (2002).
182. Drew LJ, Rohrer DK, Price MP et al. Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones. J. Physiol. 556 (Pt 3), 691-710 (2004).
183. Lu Y, Ma X, Sabharwal R et al. The ion channel ASIC2 is required for baroreceptor and autonomic control of the circulation. Neuron 64 (6), 885-897 (2009).
184. Tan ZY, Lu Y, Whiteis CA, Benson CJ, Chapleau MW, Abboud FM. Acid-sensing ion channels contribute to transduction of extracellular acidosis in rat carotid body glomus cells. Circ. Res. 101 (10), 1009-1019 (2007).
185. Hayes SG, Kindig AE, Kaufman MP. Blockade of acid sensing ion channels attenuates the exercise pressor reflex in cats. J. Physiol. 581 (Pt 3), 1271-1282 (2007).
186. McCord JL, Tsuchimochi H, Kaufman MP. Acid-sensing ion channels contribute to the metaboreceptor component of the exercise pressor reflex. Am. J. Physiol. Heart Circ. Physiol. 297 (1), H443-H449 (2009).
187. Lilley S, LeTissier P, Robbins J. The discovery and characterization of a proton-gated sodium current in rat retinal ganglion cells. J. Neurosci. 24 (5), 1013-1022 (2004).
188. 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. 24 (5), 1005-1012 (2004).
189. Brockway LM, Zhou ZH, Bubien JK, Jovov B, Benos DJ, Keyser KT. Rabbit retinal neurons and glia express a variety of ENaC/DEG subunits. Am. J. Physiol. Cell Physiol. 283 (1), C126-C134 (2002).
190. Ettaiche M, Deval E, Cougnon M, Lazdunski M, Voilley N. Silencing acid-sensing ion channel 1a alters cone-mediated retinal function. J. Neurosci. 26 (21), 5800-5809 (2006).
191. Ettaiche M, Deval E, Pagnotta S, Lazdunski M, Lingueglia E. Acid-sensing ion channel 3 in retinal function and survival. Invest. Ophthalmol. Vis. Sci. 50 (5), 2417-2426 (2009).
192. Hildebrand MS, de Silva MG, Klockars T et al. Characterisation of DRASIC in the mouse inner ear. Heart Res. 190 (1-2), 149-160 (2004).
193. Peng BG, Ahmad S, Chen S, Chen P, Price MP, 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. 24 (45), 10167-10175 (2004).
194. Ugawa S, Inagaki A, Yamamura H et al. Acid-sensing ion channel-1b in the stereocilia of mammalian cochlear hair cells. Neuroreport 17 (12), 1235-1239 (2006).
195. Zhang M, Gong N, Lu YG, Jia NL, Xu TL, Chen L. Functional characterization of acid-sensing ion channels in cultured neurons of rat inferior colliculus. Neuroscience 154 (2), 461-472 (2008).
196. (-/-) female mice with hearing deficit affects social development of pups. PLoS One 4 (8), e6508 (2009).
197. Ugawa S, Minami Y, Guo W et al. Receptor that leaves a sour taste in the mouth. Nature 395 (6702), 555-556 (1998).
198. Ugawa S, Yamamoto T, Ueda T et al. Amiloride-insensitive currents of the acid-sensing ion channel-2a (ASIC2a)/ASIC2b heteromeric sour-taste receptor channel. J. Neurosci. 23 (9), 3616-3622 (2003).
199. Richter TA, Dvoryanchikov GA, Roper SD, Chaudhari N. Acid-sensing ion channel-2 is not necessary for sour taste in mice. J. Neurosci. 24 (16), 4088-4091 (2004).
200. Lin W, Ogura T, Kinnamon SC. Acidactivated cation currents in rat vallate taste receptor cells. J. Neurophysiol. 88 (1), 133-141 (2002).
201. Liu L, Simon SA. Acidic stimuli activates two distinct pathways in taste receptor cells from rat fungiform papillae. Brain Res. 923 (1-2), 58-70 (2001).
202. Huque T, Cowart BJ, Dankulich-Nagrudny L et al. Sour ageusia in two individuals implicates ion channels of the ASIC and PKD families in human sour taste perception at the anterior tongue. PLoS One 4 (10), e7347 (2009).
203. + channel 3 and cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 281 (48), 36960-36968 (2006).
204. Agopyan N, Bhatti T, Yu S, Simon SA. Vanilloid receptor activation by 2- and 10-microm particles induces responses leading to apoptosis in human airway epithelial cells. Toxicol. Appl. Pharmacol. 192 (1), 21-35 (2003).
205. Kullmann FA, Shah MA, Birder LA, de Groat WC. Functional TRP and ASIC-like channels in cultured urothelial cells from the rat. Am. J. Physiol. Renal Physiol. 296 (4), F892-F901 (2009).
206. Huang SJ, Yang WS, Lin Y W, Wang HC, Chen CC. Increase of insulin sensitivity and reversal of age-dependent glucose intolerance with inhibition of ASIC3. Biochem. Biophys. Res. Commun. 371 (4), 729-734 (2008).
207. Jahr H, van Driel M, van Osch GJ, Weinans H, van Leeuwen JP. Identification of acid-sensing ion channels in bone. Biochem. Biophys. Res. Commun. 337 (1), 349-354 (2005).
208. Uchiyama Y, Cheng CC, Danielson KG et al. Expression of acid-sensing ion channel 3 (ASIC3) in nucleus pulposus cells of the intervertebral disc is regulated by p75NTR and ERK signaling. J. Bone Miner. Res. 22 (12), 1996-2006 (2007).
209. Kolker SJ, Walder RY, Usachev Y et al. ASIC3 expressed in Type B synoviocytes and chondrocytes modulates hyaluronan expression and release. Ann. Rheum. Dis. DOI: 10.1136/ard.2009.117168 (2009) (Epub ahead of print).
210. Drummond HA, Grifoni SC, Jernigan NL. A new trick for an old dogma: ENaC proteins as mechanotransducers in vascular smooth muscle. Physiology (Bethesda) 23, 23-31 (2008).
211. Grifoni SC, Jernigan NL, Hamilton G, Drummond HA. ASIC proteins regulate smooth muscle cell migration. Microvasc. Res. 75 (2), 202-210 (2008).
212. Grifoni SD, McKey SE, Drummond HA. Hsc70 regulates cell surface ASIC2 expression and vascular smooth muscle cell migration. Am. J. Physiol. Heart Circ. Physiol. 294 (5), H2022-H2030 (2008).
213. Gannon KP, Vanlandingham LG, Jernigan NL, Grifoni SC, Hamilton G, Drummond HA. Impaired pressure-induced constriction in mouse middle cerebral arteries of ASIC2 knockout mice. Am. J. Physiol. Heart Circ. Physiol. 294 (4), H1793-H1803 (2008).
214. Vila-Carriles WH, Kovacs GG, Jovov B et al. Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells. J. Biol. Chem. 281 (28), 19220-19232 (2006).
215. Bernardinelli L, Murgia SB, Bitti PP et al. Association between the ACCN1 gene and multiple sclerosis in Central East Sardinia. PLoS One 2 (5), e480 (2007).
216. Girirajan S, Williams SR, Garbern JY, Nowak N, Hatchwell E, Elsea SH. 17p11.2p12 triplication and del (17) q11.2q12 in a severely affected child with dup (17) p11.2p12 syndrome. Clin. Genet. 72 (1), 47-58 (2007).
217. Stone JL, Merriman B, Cantor RM, Geschwind DH, Nelson SF. High density SNP association study of a major autism linkage region on chromosome 17. Hum. Mol. Genet. 16 (6), 704-715 (2007).
218. Hettema JM, An SS, Neale MC, van den Oord EJ, Kendler KS, Chen X. Lack of association between the amiloride-sensitive cation channel 2 (ACCN2) gene and anxiety spectrum disorders. Psychiatr. Genet. 18 (2), 73-79 (2008).