Acid-sensing ion channels: potential therapeutic targets for neurologic diseases

Translational Neurodegeneration

Chun-Feng Liu²  Fen Wang¹  Xiao-Yu Cheng³  Sha Liu³ 

[1] Institute of Neuroscience, Soochow University, Suzhou 215123, China;Beijing Key Laboratory for Parkinson’s Disease, Beijing 100053, China;Department of Neurology, the Second Affiliated Hospital of Soochow University, Soochow University, 1055 Sanxiang Road, Suzhou 215004, China

关键词: Neurodegeneration;    Pathophysiology;    Neurologic diseases;    Acid sensing ionic channels;   

Others  :  1209094
DOI  :  10.1186/s40035-015-0031-3

 received in 2014-11-07, accepted in 2015-05-14,  发布年份 2015

【 摘 要 】

Maintaining the physiological pH of interstitial fluid is crucial for normal cellular functions. In disease states, tissue acidosis is a common pathologic change causing abnormal activation of acid-sensing ion channels (ASICs), which according to cumulative evidence, significantly contributes to inflammation, mitochondrial dysfunction, and other pathologic mechanisms (i.e., pain, stroke, and psychiatric conditions). Thus, it has become increasingly clear that ASICs are critical in the progression of neurologic diseases. This review is focused on the importance of ASICs as potential therapeutic targets in combating neurologic diseases.

【 授权许可】

   
2015 Liu et al.; licensee BioMed Central.

【 图 表 】

Fig. 1.

Fig. 2.

【 参考文献 】

• [1]Wemmie JA, Taugher RJ, Kreple CJ: Acid-sensing ion channels in pain and disease. Nat Rev Neurosci 2013, 14(7):461-71.
• [2]Xiong ZG, Pignataro G, Li M, Chang SY, Simon RP: Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases. Curr Opin Pharmacol 2008, 8(1):25-32.
• [3]Wemmie JA, Price MP, Welsh MJ: Acid-sensing ion channels: advances, questions and therapeutic opportunities. Trends Neurosci 2006, 29(10):578-86.
• [4]Benarroch EE: Acid-sensing cation channels: structure, function, and pathophysiologic implications. Neurology 2014, 82(7):628-35.
• [5]Sherwood TW, Frey EN, Askwith CC: Structure and activity of the acid-sensing ion channels. Am J Physiol Cell Physiol 2012, 303(7):C699-710.
• [6]Chu XP, Papasian CJ, Wang JQ, Xiong ZG: Modulation of acid-sensing ion channels: molecular mechanisms and therapeutic potential. Int J Physiol Pathophysiol Pharmacol 2011, 3(4):288-309.
• [7]Grunder S, Chen X: Structure, function, and pharmacology of acid-sensing ion channels (ASICs): focus on ASIC1a. Int J Physiol Pathophysiol Pharmacol 2010, 2(2):73-94.
• [8]Gonzales EB, Kawate T, Gouaux E: Pore architecture and ion sites in acid-sensing ion channels and P2X receptors. Nature 2009, 460(7255):599-604.
• [9]Jasti J, Furukawa H, Gonzales EB, Gouaux E: Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH. Nature 2007, 449(7160):316-23.
• [10]Grunder S, Pusch M: Biophysical properties of acid-sensing ion channels (ASICs). Neuropharmacology 2015, S0028–3908(14):00467-5.
• [11]Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M: A proton-gated cation channel involved in acid-sensing. Nature 1997, 386(6621):173-7.
• [12]Qadri YJ, Rooj AK, Fuller CM: ENaCs and ASICs as therapeutic targets. Am J Physiol Cell Physiol 2012, 302(7):C943-65.
• [13]Mari Y, Katnik C, Cuevas J: ASIC1a channels are activated by endogenous protons during ischemia and contribute to synergistic potentiation of intracellular Ca(2+) overload during ischemia and acidosis. Cell Calcium 2010, 48(1):70-82.
• [14]Kellenberger S, Schild L: International union of basic and clinical pharmacology. XCI. Structure, function, and pharmacology of acid-sensing Ion channels and the epithelial Na + channel. Pharmacol Rev 2015, 67(1):1-35.
• [15]Li M, Inoue K, Branigan D, Kratzer E, Hansen JC, Chen JW, et al.: Acid-sensing ion channels in acidosis-induced injury of human brain neurons. J Cereb Blood Flow Metab 2010, 30(6):1247-60.
• [16]Chu XP, Xiong ZG: Acid-sensing ion channels in pathological conditions. Adv Exp Med Biol 2013, 961:419-31.
• [17]Gautam M, Benson CJ, Ranier JD, Light AR, Sluka KA: ASICs do not play a role in maintaining hyperalgesia induced by repeated intramuscular acid injections. Pain Res Treat 2012, 2012:817347.
• [18]Arnett TR: Extracellular pH regulates bone cell function. J Nutr 2008, 138(2):415S-8.
• [19]Kreple CJ, Lu Y, Taugher RJ, Schwager-Gutman AL, Du J, Stump M, et al.: Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity. Nat Neurosci 2014, 17(8):1083-91.
• [20]Xiong Z, Liu Y, Hu L, Ma B, Ai Y, Xiong C: A rapid facilitation of acid-sensing ion channels current by corticosterone in cultured hippocampal neurons. Neurochem Res 2013, 38(7):1446-53.
• [21]Gautam M, Benson CJ: Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits. FASEB J 2013, 27(2):793-802.
• [22]Sluka KA, Rasmussen LA, Edgar MM, O’Donnell JM, Walder RY, Kolker SJ, et al.: Acid-sensing ion channel 3 deficiency increases inflammation but decreases pain behavior in murine arthritis. Arthritis Rheum 2013, 65(5):1194-202.
• [23]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 2008, 28(1):74-86.
• [24]Behan AT, Breen B, Hogg M, Woods I, Coughlan K, Mitchem M, et al.: Acidotoxicity and acid-sensing ion channels contribute to motoneuron degeneration. Cell Death Differ 2013, 20(4):589-98.
• [25]Liu X, He L, Dinger B, Fidone SJ: Chronic hypoxia-induced acid-sensitive ion channel expression in chemoafferent neurons contributes to chemoreceptor hypersensitivity. Am J Physiol Lung Cell Mol Physiol 2011, 301(6):L985-92.
• [26]Dorofeeva NA, Barygin OI, Staruschenko A, Bolshakov KV, Magazanik LG: Mechanisms of non-steroid anti-inflammatory drugs action on ASICs expressed in hippocampal interneurons. J Neurochem 2008, 106(1):429-41.
• [27]Voilley N, de Weille J, Mamet J, Lazdunski M: Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci 2001, 21(20):8026-33.
• [28]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 2004, 3(1):71-9.
• [29]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 2003, 12(7):1332-43.
• [30]Salinas M, Rash LD, Baron A, Lambeau G, Escoubas P, Lazdunski M: The receptor site of the spider toxin PcTx1 on the proton-gated cation channel ASIC1a. J Physiol 2006, 570(Pt 2):339-54.
• [31]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 2009, 284(26):17625-33.
• [32]Delaunay A, Gasull X, Salinas M, Noël J, Friend V, Lingueglia E, et al.: Human ASIC3 channel dynamically adapts its activity to sense the extracellular pH in both acidic and alkaline directions. Proc Natl Acad Sci U S A 2012, 109(32):13124-9.
• [33]Anangi R, Rash LD, Mobli M, King GF: Functional expression in Escherichia coli of the disulfide-rich sea anemone peptide APETx2, a potent blocker of acid-sensing ion channel 3. Mar Drugs 2012, 10(7):1605-18.
• [34]Deval E, Noel J, Gasull X, Delaunay A, Alloui A, Friend V, et al.: Acid-sensing ion channels in postoperative pain. J Neurosci 2011, 31(16):6059-66.
• [35]Bohlen CJ, Chesler AT, Sharif-Naeini R, Medzihradszky KF, Zhou S, King D, et al.: A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain. Nature 2011, 479(7373):410-4.
• [36]Baron A, Diochot S, Salinas M, Deval E, Noël J, Lingueglia E: Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels. Toxicon 2013, 75:187-204.
• [37]Yu Y, Chen Z, Li WG, Cao H, Feng EG, Yu F, et al.: A nonproton ligand sensor in the acid-sensing ion channel. Neuron 2010, 68(1):61-72.
• [38]Rodriguez AA, Salceda E, Garateix AG, Zaharenko AJ, Peigneur S, López O, et al.: A novel sea anemone peptide that inhibits acid-sensing ion channels. Peptides 2014, 53:3-12.
• [39]Duan B, Wang YZ, Yang T, Chu XP, Yu Y, Huang Y, et al.: Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis. J Neurosci 2011, 31(6):2101-12.
• [40]Li WG, Yu Y, Zhang ZD, Cao H, Xu TL: ASIC3 channels integrate agmatine and multiple inflammatory signals through the nonproton ligand sensing domain. Mol Pain 2010, 6:88. BioMed Central Full Text
• [41]Diochot S, Baron A, Salinas M, Douguet D, Scarzello S, Dabert-Gay AS, et al.: Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature 2012, 490(7421):552-5.
• [42]Muto S, Imai M, Asano Y: Effect of nafamostat mesilate on Na + and K+ transport properties in the rabbit cortical collecting duct. Br J Pharmacol 1993, 109(3):673-8.
• [43]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 2007, 363(1):203-8.
• [44]Zha XM: Acid-sensing ion channels: trafficking and synaptic function. Mol Brain 2013, 6:1. BioMed Central Full Text
• [45]Wu PY, Huang YY, Chen CC, Hsu TT, Lin YC, Weng JY, et al.: Acid-sensing ion channel-1a is not required for normal hippocampal LTP and spatial memory. J Neurosci 2013, 33(5):1828-32.
• [46]Magnotta VA, Heo HY, Dlouhy BJ, Dahdaleh NS, Follmer RL, Thedens DR, et al.: Detecting activity-evoked pH changes in human brain. Proc Natl Acad Sci U S A 2012, 109(21):8270-3.
• [47]Chu XP, Miesch J, Johnson M, Root L, Zhu XM, Chen D, et al.: Proton-gated channels in PC12 cells. J Neurophysiol 2002, 87(5):2555-61.
• [48]Wang YZ, Xu TL: Acidosis, acid-sensing ion channels, and neuronal cell death. Mol Neurobiol 2011, 44(3):350-8.
• [49]Wang YZ, Zeng WZ, Xiao X, Huang Y, Song XL, Yu Z, et al.: Intracellular ASIC1a regulates mitochondrial permeability transition-dependent neuronal death. Cell Death Differ 2013, 20(10):1359-69.
• [50]Arias RL, Sung ML, Vasylyev D, Zhang MY, Albinson K, Kubek K, et al.: Amiloride is neuroprotective in an MPTP model of Parkinson’s disease. Neurobiol Dis 2008, 31(3):334-41.
• [51]Joch M, Ase AR, Chen CX, MacDonald PA, Kontogiannea M, Corera AT, et al.: Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels. Mol Biol Cell 2007, 18(8):3105-18.
• [52]Yu XW, Hu ZL, Ni M, Fang P, Zhang PW, Shu Q, et al.: Acid-sensing ion channels promote the inflammation and migration of cultured rat microglia. Glia 2014, 63(3):483-96.
• [53]Wong HK, Bauer PO, Kurosawa M, Goswami A, Washizu C, Machida Y, et al.: Blocking acid-sensing ion channel 1 alleviates Huntington’s disease pathology via an ubiquitin-proteasome system-dependent mechanism. Hum Mol Genet 2008, 17(20):3223-35.
• [54]Jensen JE, Cristofori-Armstrong B, Anangi R, Anangi R, Rosengren KJ, Lau CH, et al.: Understanding the molecular basis of toxin promiscuity: the analgesic sea anemone peptide APETx2 interacts with acid-sensing ion channel 3 and hERG channels via overlapping pharmacophores. J Med Chem 2014, 57(21):9195-203.
• [55]Page AJ, Brierley SM, Martin CM, Price MP, Symonds E, Butler R, et al.: Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function. Gut 2005, 54(10):1408-15.
• [56]Lingueglia E: Acid-Sensing Ion Channels (ASICs) in pain. Biol Aujourdhui 2014, 208(1):13-20.
• [57]Mishra V, Verma R, Raghubir R: Neuroprotective effect of flurbiprofen in focal cerebral ischemia: the possible role of ASIC1a. Neuropharmacology 2010, 59(7–8):582-8.
• [58]Duan B, Wu LJ, Yu YQ, Ding Y, Jing L, Xu L, et al.: Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity. J Neurosci 2007, 27(41):11139-48.
• [59]Wu LJ, Duan B, Mei YD, Gao J, Chen JG, Zhuo M, et al.: Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord. J Biol Chem 2004, 279(42):43716-24.
• [60]Duan B, Liu DS, Huang Y, Zeng WZ, Wang X, Yu H, et al.: PI3-kinase/Akt pathway-regulated membrane insertion of acid-sensing ion channel 1a underlies BDNF-induced pain hypersensitivity. J Neurosci 2012, 32(18):6351-63.
• [61]Dawson RJ, Benz J, Stohler P, Tetaz T, Joseph C, Huber S, et al.: Structure of the acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1. Nat Commun. 2012, 3:936.
• [62]Gao J, Duan B, Wang DG, Deng XH, Zhang GY, Xu L, et al.: Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death. Neuron 2005, 48(4):635-46.
• [63]Zhang Y, Zhou L, Zhang X, Bai J, Shi M, Zhao G: Ginsenoside-Rd attenuates TRPM7 and ASIC1a but promotes ASIC2a expression in rats after focal cerebral ischemia. Neurol Sci 2012, 33(5):1125-31.
• [64]Gu L, Yang Y, Sun Y, Zheng X: Puerarin inhibits acid-sensing ion channels and protects against neuron death induced by acidosis. Planta Med 2010, 76(6):583-8.
• [65]Yan J, Dussor G: Ion channels and migraine. Headache 2014, 54(4):619-39.
• [66]Dussor G: ASICs as therapeutic targets for migraine. Neuropharmacology. 2015, S0028–3908(14):00466-3.
• [67]Tso AR, Goadsby PJ: New targets for migraine therapy. Curr Treat Options Neurol 2014, 16(11):318.
• [68]Durham PL, Masterson CG: Two mechanisms involved in trigeminal CGRP release: implications for migraine treatment. Headache 2013, 53(1):67-80.
• [69]Holland PR, Akerman S, Andreou AP, Karsan N, Wemmie JA, Goadsby PJ: Acid-sensing ion channel 1: a novel therapeutic target for migraine with aura. Ann Neurol 2012, 72(4):559-63.
• [70]Vergo S, Craner MJ, Etzensperger R, Attfield K, Friese MA, Newcombe J, et al.: Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model. Brain 2011, 134(Pt 2):571-84.
• [71]Friese MA, Craner MJ, Etzensperger R, Vergo S, Wemmie JA, Welsh MJ, et al.: Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system. Nat Med 2007, 13(12):1483-9.
• [72]Arun T, Tomassini V, Sbardella E, de Ruiter MB, Matthews L, Leite MI, et al.: Targeting ASIC1 in primary progressive multiple sclerosis: evidence of neuroprotection with amiloride. Brain 2013, 136(Pt 1):106-15.
• [73]McKhann GM 2nd: Seizure termination by acidosis depends on ASIC1a. Neurosurgery 2008, 63(4):N10.
• [74]N’Gouemo P: Amiloride delays the onset of pilocarpine-induced seizures in rats. Brain Res 2008, 1222:230-2.
• [75]Ziemann AE, Schnizler MK, Albert GW, Severson MA, Howard MA III, Welsh MJ, et al.: Seizure termination by acidosis depends on ASIC1a. Nat Neurosci 2008, 11(7):816-22.
• [76]Berdiev BK, Xia J, McLean LA, Markert JM, Gillespie GY, Mapstone TB, et al.: Acid-sensing ion channels in malignant gliomas. J Biol Chem 2003, 278(17):15023-34.
• [77]Rooj AK, McNicholas CM, Bartoszewski R, Bebok Z, Benos DJ, Fuller CM: Glioma-specific cation conductance regulates migration and cell cycle progression. J Biol Chem 2012, 287(6):4053-65.
• [78]Kapoor N, Bartoszewski R, Qadri YJ, Bebok Z, Bubien JK, Fuller CM, et al.: Knockdown of ASIC1 and epithelial sodium channel subunits inhibits glioblastoma whole cell current and cell migration. J Biol Chem 2009, 284(36):24526-41.