Abstract
Acidosis is a noxious condition associated with inflammation, ischaemia or defective acid containment. As a consequence, acid sensing has evolved as an important property of afferent neurons with unmyelinated and thinly myelinated nerve fibres. Protons evoke multiple currents in primary afferent neurons, which are carried by several acid-sensitive ion channels. Among these, acid-sensing ion channels (ASICs) and transient receptor potential (TRP) vanilloid-1 (TRPV1) ion channels have been most thoroughly studied. ASICs survey moderate decreases in extracellular pH, whereas TRPV1 is activated only by severe acidosis resulting in pH values below 6. Two-pore-domain K+ (K2P) channels are differentially regulated by small deviations of extra- or intracellular pH from physiological levels. Other acid-sensitive channels include TRPV4, TRPC4, TRPC5, TRPP2 (PKD2L1), ionotropic purinoceptors (P2X), inward rectifier K+ channels, voltage-activated K+ channels, L-type Ca2+ channels, hyperpolarization-activated cyclic nucleotide gated channels, gap junction channels, and Cl− channels. In addition, acid-sensitive G protein coupled receptors have also been identified. Most of these molecular acid sensors are expressed by primary sensory neurons, although to different degrees and in various combinations. Emerging evidence indicates that many of the acid-sensitive ion channels and receptors play a role in acid sensing, acid–induced pain and acid-evoked feedback regulation of homeostatic reactions. The existence and apparent redundancy of multiple pH surveillance systems attests to the concept that acid–base regulation is a vital issue for cell and tissue homeostasis. Since upregulation and overactivity of acid sensors appear to contribute to various forms of chronic pain, acid-sensitive ion channels and receptors are considered as targets for novel analgesic drugs. This approach will only be successful if the pathological implications of acid sensors can be differentiated pharmacologically from their physiological function.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aihara E, Hayashi M, Sasaki Y, Kobata A, Takeuchi K (2005) Mechanisms underlying capsaicin-stimulated secretion in the stomach: comparison with mucosal acidification. J Pharmacol Exp Ther 315:423–432
Akiba Y, Takeuchi T, Mizumori M, Guth PH, Engel E, Kaunitz JD (2006a) TRPV-1 knockout paradoxically protects mouse gastric mucosa from acid/ethanol-induced injury by upregulating compensatory protective mechanisms. Gastroenterology 130(Suppl 2):A–106
Akiba Y, Ghayouri S, Takeuchi T, Mizumori M, Guth PH, Engel E, Swenson ER, Kaunitz JD (2006b) Carbonic anhydrases and mucosal vanilloid receptors help mediate the hyperemic response to luminal CO2 in rat duodenum. Gastroenterology 131:142–152
Alvarez de la Rosa D, Zhang P, Shao D, White F, Canessa CM (2002) Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. Proc Natl Acad Sci USA 99:2326–2331
Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford AP, Davis JB, Dasgupta P, Fowler CJ, Anand P (2005) Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol 174:977–982
Askwith CC, Cheng C, Ikuma M, Benson C, Price MP, Welsh MJ (2000) Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels. Neuron 26:133–141
Auzanneau C, Thoreau V, Kitzis A, Becq F (2003) A novel voltage-dependent chloride current activated by extracellular acidic pH in cultured rat Sertoli cells. J Biol Chem 278:19230–19236
Auzanneau C, Norez C, Antigny F, Thoreau V, Jougla C, Cantereau A, Becq F, Vandebrouck C (2008) Transient receptor potential vanilloid 1 (TRPV1) channels in cultured rat Sertoli cells regulate an acid sensing chloride channel. Biochem Pharmacol 75:476–483
Avelino A, Cruz F (2006) TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications. Naunyn Schmiedebergs Arch Pharmacol 373:287–299
Banerjee B, Medda BK, Lazarova Z, Bansal N, Shaker R, Sengupta JN (2007) Effect of reflux-induced inflammation on transient receptor potential vanilloid one (TRPV1) expression in primary sensory neurons innervating the oesophagus of rats. Neurogastroenterol Motil 19:681–691
Bang H, Kim Y, Kim D (2000) TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family. J Biol Chem 275:17412–17419
Baumann TK, Chaudhary P, Martenson ME (2004) Background potassium channel block and TRPV1 activation contribute to proton depolarization of sensory neurons from humans with neuropathic pain. Eur J Neurosci 19:1343–1351
Bayliss DA, Talley EM, Sirois JE, Lei Q (2001) TASK-1 is a highly modulated pH-sensitive ‘leak’ K+ channel expressed in brainstem respiratory neurons. Respir Physiol 129:159–174
Bearzatto B, Lesage F, Reyes R, Lazdunski M, Laduron PM (2000) Axonal transport of TREK and TRAAK potassium channels in rat sciatic nerves. Neuroreport 11:927–930
Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R (2004) Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. Br J Pharmacol 141:737–745
Benson CJ, Eckert SP, McCleskey EW (1999) Acid-evoked currents in cardiac sensory neurons: a possible mediator of myocardial ischemic sensation. Circ Res 84:921–928
Benson CJ, Xie J, Wemmie JA, Price MP, Henss JM, Welsh MJ, Snyder PM (2002) Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons. Proc Natl Acad Sci USA 99:2338–2343
Bertrand PP, Kunze WA, Bornstein JC, Furness JB, Smith ML (1997) Analysis of the responses of myenteric neurons in the small intestine to chemical stimulation of the mucosa. Am J Physiol 273:G422–G435
Bevan S, Geppetti P (1994) Protons: small stimulants of capsaicin-sensitive sensory nerves. Trends Neurosci 17:509–512
Bevan S, Yeats J (1991) Protons activate a cation conductance in a sub-population of rat dorsal root ganglion neurones. J Physiol (Lond) 433:145–161
Bhat YM, Bielefeldt K (2006) Capsaicin receptor (TRPV1) and non-erosive reflux disease. Eur J Gastroenterol Hepatol 18:263–270
Bhattacharya A, Scott BP, Nasser N, Ao H, Maher MP, Dubin AE, Swanson DM, Shankley NP, Wickenden AD, Chaplan SR (2007) Pharmacology and antitussive efficacy of 4-(3-trifluoromethyl-pyridin-2-yl)-piperazine-1-carboxylic acid (5-trifluoromethyl-pyridin-2-yl)-amide (JNJ17203212), a transient receptor potential vanilloid 1 antagonist in guinea pigs. J Pharmacol Exp Ther 323:665–674
Bielefeldt K, Davis BM (2008) Differential effects of ASIC3 and TRPV1 deletion on gastroesophageal sensation in mice. Am J Physiol 294:G130–G138
Bina RW, Hempleman SC (2007) Evidence for TREK-like tandem-pore domain channels in intrapulmonary chemoreceptor chemotransduction. Respir Physiol Neurobiol 156:120–131
Birder LA, Kanai AJ, de Groat WC, Kiss S, Nealen ML, Burke NE, Dineley KE, Watkins S, Reynolds IJ, Caterina MJ (2001) Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci USA 98:13396–13401
Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ, Wang E, Ruiz G, De Groat WC, Apodaca G, Watkins S, Caterina MJ (2002) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5:856–860
Bley KR (2004) Recent developments in transient receptor potential vanilloid receptor 1 agonist-based therapies. Expert Opin Investig Drugs 13:1445–1456
Brady CM, Apostolidis AN, Harper M, Yiangou Y, Beckett A, Jacques TS, Freeman A, Scaravilli F, Fowler CJ, Anand P (2004) Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment. BJU Int 93:770–776
Breese NM, George AC, Pauers LE, Stucky CL (2005) Peripheral inflammation selectively increases TRPV1 function in IB4-positive sensory neurons from adult mouse. Pain 115:37–49
Brown SG, Townsend-Nicholson A, Jacobson KA, Burnstock G, King BF (2002) Heteromultimeric P2X1/2 receptors show a novel sensitivity to extracellular pH. J Pharmacol Exp Ther 300:673–680
Buckler KJ (2007) TASK-like potassium channels and oxygen sensing in the carotid body. Respir Physiol Neurobiol 157:55–64
Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797
Cadiou H, Studer M, Jones NG, Smith ES, Ballard A, McMahon SB, McNaughton PA (2007) Modulation of acid-sensing ion channel activity by nitric oxide. J Neurosci 27:13251–13260
Campanucci VA, Fearon IM, Nurse CA (2003) A novel O2-sensing mechanism in rat glossopharyngeal neurones mediated by a halothane-inhibitable background K+ conductance. J Physiol (Lond) 548:731–743
Canning BJ, Farmer DG, Mori N (2006) Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs. Am J Physiol 291:R454–R463
Carlton SM, Coggeshall RE (2001) Peripheral capsaicin receptors increase in the inflamed rat hindpaw: a possible mechanism for peripheral sensitization. Neurosci Lett 310:53–56
Catarsi S, Babinski K, Séguéla P (2001) Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF. Neuropharmacology 41:592–600
Caterina MJ, Julius D (2001) The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 24:487–517
Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824
Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313
Chan CL, Facer P, Davis JB, Smith GD, Egerton J, Bountra C, Williams NS, Anand P (2003) Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency. Lancet 361:385–391
Chandrashekar J, Hoon MA, Ryba NJ, Zuker CS (2006) The receptors and cells for mammalian taste. Nature 444:288–294
Chapman CG, Meadows HJ, Godden RJ, Campbell DA, Duckworth M, Kelsell RE, Murdock PR, Randall AD, Rennie GI, Gloger IS (2000) Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel. Mol Brain Res 82:74–83
Chavez RA, Gray AT, Zhao BB, Kindler CH, Mazurek MJ, Mehta Y, Forsayeth JR, Yost CS (1999) TWIK-2, a new weak inward rectifying member of the tandem pore domain potassium channel family. J Biol Chem 274:7887–7892
Chen CC, England S, Akopian AN, Wood JN (1998) A sensory neuron-specific, proton-gated ion channel. Proc Natl Acad Sci USA 95:10240–10245
Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, Zimmer A (2002) A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc Natl Acad Sci USA 99:8992–8997
Chizh BA, Illes P (2001) P2X receptors and nociception. Pharmacol Rev 53:553–568
Chuang YC, Chancellor MB, Seki S, Yoshimura N, Tyagi P, Huang L, Lavelle JP, De Groat WC, Fraser MO (2003) Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity. Urology 61:664–670
Chuang YC, Yoshimura N, Huang CC, Chiang PH, Chancellor MB (2004) Intravesical botulinum toxin a administration produces analgesia against acetic acid induced bladder pain responses in rats. J Urol 172:1529–1532
Clapham DE, Julius D, Montell C, Schultz G (2005) International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol Rev 57:427–450
Clarke GD, Davison JS (1978) Mucosal receptors in the gastric antrum and small intestine of the rat with afferent fibres in the cervical vagus. J Physiol (Lond) 284:55–67
Clarke CE, Benham CD, Bridges A, George AR, Meadows HJ (2000) Mutation of histidine 286 of the human P2X4 purinoceptor removes extracellular pH sensitivity. J Physiol (Lond) 523:697–703
Claydon TW, Boyett MR, Sivaprasadarao A, Orchard CH (2000) Two pore residues mediate acidosis-induced enhancement of C-type inactivation of the Kv1.4 K+ channel. Am J Physiol 283:C1114–C1121
Clyne JD, LaPointe LD, Hume RI (2002) The role of histidine residues in modulation of the rat P2X2 purinoceptor by zinc and pH. J Physiol (Lond) 539:347–359
Cockayne DA, Hamilton SG, Zhu QM, Dunn PM, Zhong Y, Novakovic S, Malmberg AB, Cain G, Berson A, Kassotakis L, Hedley L, Lachnit WG, Burnstock G, McMahon SB, Ford AP (2000) Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 407:1011–1015
Cockayne DA, Dunn PM, Zhong Y, Rong W, Hamilton SG, Knight GE, Ruan HZ, Ma B, Yip P, Nunn P, McMahon SB, Burnstock G, Ford AP (2005) P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. J Physiol (2005) 567:621–639
Coffin B, Chollet R, Flourie B, Lemann M, Franchisseur C, Rambaud JC, Jian R (2001) Intraluminal modulation of gastric sensitivity to distension: effects of hydrochloric acid and meal. Am J Physiol 280:G904–G909
Cooper BY, Johnson RD, Rau KK (2004) Characterization and function of TWIK-related acid sensing K+ channels in a rat nociceptive cell. Neuroscience 129:209–224
Cruz F, Dinis P (2007) Resiniferatoxin and botulinum toxin type A for treatment of lower urinary tract symptoms. Neurourol Urodyn 26(6 suppl):920–927
Daly D, Rong W, Chess-Williams R, Chapple C, Grundy D (2007) Bladder afferent sensitivity in wild-type and TRPV1 knockout mice. J Physiol (Lond) 583:663–674
Dang K, Bielefeldt K, Gebhart GF (2005) Differential responses of bladder lumbosacral and thoracolumbar dorsal root ganglion neurons to purinergic agonists, protons, and capsaicin. J Neurosci 25:3973–3984
Danzer M, Jocic M, Samberger C, Painsipp E, Bock E, Pabst MA, Crailsheim K, Schicho R, Lippe IT, Holzer P (2004) Stomach-brain communication by vagal afferents in response to luminal acid backdiffusion, gastrin, and gastric acid secretion. Am J Physiol 286:G403–G411
Davies NW, Lux HD, Morad M (1988) Site and mechanism of activation of proton-induced sodium current in chick dorsal root ganglion neurones. J Physiol (Lond) 400:159–187
Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183–187
Delmas P (2005) Polycystins: polymodal receptor/ion-channel cellular sensors. Pflügers Arch 451:264–276
Dean JB, Ballantyne D, Cardone DL, Erlichman JS, Solomon IC (2002) Role of gap junctions in CO2 chemoreception and respiratory control. Am J Physiol 283:L665–L670
Decher N, Maier M, Dittrich W, Gassenhuber J, Bruggemann A, Busch AE, Steinmeyer K (2001) Characterization of TASK-4, a novel member of the pH-sensitive, two-pore domain potassium channel family. FEBS Lett 492:84–89
Deval E, Baron A, Lingueglia E, Mazarguil H, Zajac JM, Lazdunski M (2003) Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability. Neuropharmacology 44:662–671
Ding S, Sachs F (1999) Single channel properties of P2X2 purinoceptors. J Gen Physiol 113:695–720
Diochot S, Baron A, Rash LD, Deval E, Escoubas P, Scarzello S, Salinas M, Lazdunski M (2004) A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. EMBO J 23:1516–1525
Diochot S, Salinas M, Baron A, Escoubas P, Lazdunski M (2007) Peptides inhibitors of acid-sensing ion channels. Toxicon 49:271–284
Dobler T, Springauf A, Tovornik S, Weber M, Schmitt A, Sedlmeier R, Wischmeyer E, Döring F (2007) TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones. J Physiol (Lond) 585:867–879
Docherty RJ, Yeats JC, Piper AS (1997) Capsazepine block of voltage-activated calcium channels in adult rat dorsal root ganglion neurones in culture. Br J Pharmacol 121:1461–1467
Drewes AM, Schipper KP, Dimcevski G, Petersen P, Gregersen H, Funch-Jensen P, Arendt-Nielsen L (2003) Gut pain and hyperalgesia induced by capsaicin: a human experimental model. Pain 104:333–341
Duan B, Wu LJ, Yu YQ, Ding Y, Jing L, Xu L, Chen J, Xu TL (2007) Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity. J Neurosci 27:11139–11148
Dubé GR, Lehto SG, Breese NM, Baker SJ, Wang X, Matulenko MA, Honoré P, Stewart AO, Moreland RB, Brioni JD (2005) Electrophysiological and in vivo characterization of A-317567, a novel blocker of acid sensing ion channels. Pain 117:88–96
Dunn PM, Zhong Y, Burnstock G (2001) P2X receptors in peripheral neurons. Prog Neurobiol 65:107–134
Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M (1997) TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J 16:5464–5471
Duprat F, Girard C, Jarretou G, Lazdunski M (2005) Pancreatic two P domain K+ channels TALK-1 and TALK-2 are activated by nitric oxide and reactive oxygen species. J Physiol (Lond) 562:235–244
Duprat F, Lauritzen I, Patel A, Honoré E (2007) The TASK background K2P channels: chemo- and nutrient sensors. Trends Neurosci 30:573–580
Escoubas P, De Weille JR, Lecoq A, Diochot S, Waldmann R, Champigny G, Moinier D, Menez A, Lazdunski M (2000) Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels. J Biol Chem 275:25116–25121
Faisy C, Planquette B, Naline E, Risse PA, Frossard N, Fagon JY, Advenier C, Devillier P (2007) Acid-induced modulation of airway basal tone and contractility: role of acid-sensing ion channels (ASICs) and TRPV1 receptor. Life Sci 81:1094–1102
Fallingborg J (1999) Intraluminal pH of the human gastrointestinal tract. Dan Med Bull 46:183–196
Filosa JA, Putnam RW (2003) Multiple targets of chemosensitive signaling in locus coeruleus neurons: role of K+ and Ca2+ channels. Am J Physiol 284:C145–C155
Fischer MJ, Reeh PW, Sauer SK (2003) Proton-induced calcitonin gene-related peptide release from rat sciatic nerve axons, in vitro, involving TRPV1. Eur J Neurosci 18:803–810
Forster ER, Green T, Elliot M, Bremner A, Dockray GJ (1990) Gastric emptying in rats: role of afferent neurons and cholecystokinin. Am J Physiol 258:G552–G556
Friese MA, Craner MJ, Etzensperger R, Vergo S, Wemmie JA, Welsh MJ, Vincent A, Fugger L (2007) Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system. Nat Med 13:1483–1489
Fujino K, de la Fuente SG, Takami Y, Takahashi T, Mantyh CR (2006) Attenuation of acid induced oesophagitis in VR-1 deficient mice. Gut 55:34–40
Fukuda T, Ichikawa H, Terayama R, Yamaai T, Kuboki T, Sugimoto T (2006) ASIC3-immunoreactive neurons in the rat vagal and glossopharyngeal sensory ganglia. Brain Res 1081:150–155
Gabriel A, Abdallah M, Yost CS, Winegar BD, Kindler CH (2002) Localization of the tandem pore domain K+ channel KCNK5 (TASK-2) in the rat central nervous system. Mol Brain Res 98:153–163
Gao Z, Henig O, Kehoe V, Sinoway LI, Li J (2006) Vanilloid type 1 receptor and the acid-sensing ion channel mediate acid phosphate activation of muscle afferent nerves in rats. J Appl Physiol 100:421–426
Gao Z, Li JD, Sinoway LI, Li J (2007a) Effect of muscle interstitial pH on P2X and TRPV1 receptor-mediated pressor response. J Appl Physiol 102:2288–2293
Gao Y, Liu SS, Qiu S, Cheng W, Zheng J, Luo JH (2007b) Fluorescence resonance energy transfer analysis of subunit assembly of the ASIC channel. Biochem Biophys Res Commun 359:143–150
García-Martínez C, Fernández-Carvajal A, Valenzuela B, Gomis A, Van Den Nest W, Ferroni S, Carreño C, Belmonte C, Ferrer-Montiel A (2006) Design and characterization of a noncompetitive antagonist of the transient receptor potential vanilloid subunit 1 channel with in vivo analgesic and anti-inflammatory activity. J Pain 7:735–746
García-Sanz N, Fernández-Carvajal A, Morenilla-Palao C, Planells-Cases R, Fajardo-Sánchez E, Fernández-Ballester G, Ferrer-Montiel A (2004) Identification of a tetramerization domain in the C terminus of the vanilloid receptor. J Neurosci 24:5307–5314
Gavva NR, Klionsky L, Qu Y, Shi L, Tamir R, Edenson S, Zhang TJ, Viswanadhan VN, Toth A, Pearce LV, Vanderah TW, Porreca F, Blumberg PM, Lile J, Sun Y, Wild K, Louis JC, Treanor JJ (2004) Molecular determinants of vanilloid sensitivity in TRPV1. J Biol Chem 279:20283–20295
Gavva NR, Tamir R, Klionsky L, Norman MH, Louis JC, Wild KD, Treanor JJ (2005a) Proton activation does not alter antagonist interaction with the capsaicin-binding pocket of TRPV1. Mol Pharmacol 68:1524–1533
Gavva NR, Tamir R, Qu Y, Klionsky L, Zhang TJ, Immke D, Wang J, Zhu D, Vanderah TW, Porreca F, Doherty EM, Norman MH, Wild KD, Bannon AW, Louis JC, Treanor JJ (2005b) AMG 9810 [(E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide], a novel vanilloid receptor 1 (TRPV1) antagonist with antihyperalgesic properties. J Pharmacol Exp Ther 313:474–484
Gavva NR, Bannon AW, Surapaneni S, Hovland DN Jr, Lehto SG, Gore A, Juan T, Deng H, Han B, Klionsky L, Kuang R, Le A, Tamir R, Wang J, Youngblood B, Zhu D, Norman MH, Magal E, Treanor JJ, Louis JC (2007) The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J Neurosci 27:3366–3374
Gavva NR, Treanor JJ, Garami A, Fang L, Surapaneni S, Akrami A, Alvarez F, Bak A, Darling M, Gore A, Jang GR, Kesslak JP, Ni L, Norman MH, Palluconi G, Rose MJ, Salfi M, Tan E, Romanovsky AA, Banfield C, Davar G (2008) Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain 136:202–210
Geppetti P, Tramontana M, Evangelista S, Renzi D, Maggi CA, Fusco BM, Del Bianco E (1991) Differential effect on neuropeptide release of different concentrations of hydrogen ions on afferent and intrinsic neurons of the rat stomach. Gastroenterology 101:1505–1511
Gerevich Z, Zadori ZS, Köles L, Kopp L, Milius D, Wirkner K, Gyires K, Illes P (2007) Dual effect of acid pH on purinergic P2X3 receptors depends on the histidine 206 residue. J Biol Chem 282:33949–33957
Gharat LA, Szallasi A (2008) Advances in the design and therapeutic use of capsaicin receptor TRPV1 agonists and antagonists. Expert Opin Ther Patents 18:159–209
Ghilardi JR, Röhrich H, Lindsay TH, Sevcik MA, Schwei MJ, Kubota K, Halvorson KG, Poblete J, Chaplan SR, Dubin AE, Carruthers NI, Swanson D, Kuskowski M, Flores CM, Julius D, Mantyh PW (2005) Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci 25:3126–3131
Girard C, Duprat F, Terrenoire C, Tinel N, Fosset M, Romey G, Lazdunski M, Lesage F (2001) Genomic and functional characteristics of novel human pancreatic 2P domain K+ channels. Biochem Biophys Res Commun 282:249–256
Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N (2001) Potassium leak channels and the KCNK family of two-P-domain subunits. Nat Rev Neurosci 2:175–184
Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S (2005) International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels. Pharmacol Rev 57:527–540
Goodis HE, Poon A, Hargreaves KM (2006) Tissue pH and temperature regulate pulpal nociceptors. J Dent Res 85:1046–1049
Groth M, Helbig T, Grau V, Kummer W, Haberberger RV (2006) Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels. Respir Res 7:96
Gu Q, Lee LY (2006) Characterization of acid signaling in rat vagal pulmonary sensory neurons. Am J Physiol 291:L58–L65
Gu W, Schlichthörl G, Hirsch JR, Engels H, Karschin C, Karschin A, Derst C, Steinlein OK, Daut J (2002) Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2. J Physiol (Lond) 539:657–668
Güler AD, Lee H, Iida T, Shimizu I, Tominaga M, Caterina M (2002) Heat-evoked activation of the ion channel, TRPV4. J Neurosci 22:6408–6414
Gunthorpe MJ, Benham CD, Randall A, Davis JB (2002) The diversity in the vanilloid (TRPV) receptor family of ion channels. Trends Pharmacol Sci 23:183–191
Gunthorpe MJ, Rami HK, Jerman JC, Smart D, Gill CH, Soffin EM, Luis Hannan S, Lappin SC, Egerton J, Smith GD, Worby A, Howett L, Owen D, Nasir S, Davies CH, Thompson M, Wyman PA, Randall AD, Davis JB (2004) Identification and characterisation of SB-366791, a potent and selective vanilloid receptor (VR1/TRPV1) antagonist. Neuropharmacology 46:133–149
Guo A, Vulchanova L, Wang J, Li X, Elde R (1999) Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. Eur J Neurosci 11:946–958
Hamilton SG, McMahon SB, Lewin GR (2001) Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin. J Physiol (Lond) 534:437–445
Han J, Kang D, Kim D (2003) Functional properties of four splice variants of a human pancreatic tandem-pore K+ channel, TALK-1. Am J Physiol 285:C529–C538
Hayes SG, Kindig AE, Kaufman MP (2007) Blockade of acid sensing ion channels attenuates the exercise pressor reflex in cats. J Physiol 581:1271–1282
Hellwig N, Plant TD, Janson W, Schäfer M, Schultz G, Schaefer M (2004) TRPV1 acts as proton channel to induce acidification in nociceptive neurons. J Biol Chem 279:34553–34561
Hervieu GJ, Cluderay JE, Gray CW, Green PJ, Ranson JL, Randall AD, Meadows HJ (2001) Distribution and expression of TREK-1, a two-pore-domain potassium channel, in the adult rat CNS. Neuroscience 103:899–919
Hicks GA (2006) TRP channels as therapeutic targets: hot property, or time to cool down? Neurogastroenterol Motil 18:590–594
Hoheisel U, Reinöhl J, Unger T, Mense S (2004) Acidic pH and capsaicin activate mechanosensitive group IV muscle receptors in the rat. Pain 110:149–157
Holzer P (1988) Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides Neuroscience 24:739–768
Holzer P (1991) Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 43:143–201
Holzer P (1998) Neural emergency system in the stomach. Gastroenterology 114:823–839
Holzer P (2003) Acid-sensitive ion channels in gastrointestinal function. Curr Opin Pharmacol 3:618–625
Holzer P (2004a) TRPV1 and the gut: from a tasty receptor for a painful vanilloid to a key player in hyperalgesia. Eur J Pharmacol 500:231–241
Holzer P (2004b) Vanilloid receptor TRPV1: hot on the tongue and inflaming the colon. Neurogastroenterol Motil 16:697–699
Holzer P (2007) Taste receptors in the gastrointestinal tract. V. Acid sensing in the gastrointestinal tract. Am J Physiol 292:G699–G705
Holzer P, Maggi CA (1998) Dissociation of dorsal root ganglion neurons into afferent and efferent-like neurons. Neuroscience 86:389–398
Holzer P, Painsipp E, Jocic M, Heinemann A (2003) Acid challenge delays gastric pressure adaptation, blocks gastric emptying and stimulates gastric fluid secretion in the rat. Neurogastroenterol Motil 15:45–55
Holzer P, Wultsch T, Edelsbrunner M, Mitrovic M, Shahbazian A, Painsipp E, Bock E, Pabst MA (2007) Increase in gastric acid-induced afferent input to the brainstem in mice with gastritis. Neuroscience 145:1108–1119
Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB, O'Keefe PF, Ramnaraine ML, Clohisy DR, Mantyh PW (2000) Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med 6:521–528
Honore P, Mikusa J, Bianchi B, McDonald H, Cartmell J, Faltynek C, Jarvis MF (2002) TNP-ATP, a potent P2X3 receptor antagonist, blocks acetic acid-induced abdominal constriction in mice: comparison with reference analgesics. Pain 96:99–105
Honoré E, Maingret F, Lazdunski M, Patel AJ (2002) An intracellular proton sensor commands lipid- and mechano-gating of the K+ channel TREK-1. EMBO J 21:2968–2976
Huang AL, Chen X, Hoon MA, Chandrashekar J, Guo W, Tränkner D, Ryba NJ, Zuker CS (2006) The cells and logic for mammalian sour taste detection. Nature 442:934–938
Huang CW, Tzeng JN, Chen YJ, Tsai WF, Chen CC, Sun WH (2007) Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors. Mol Cell Neurosci 36:195–210
Hughes PA, Brierley SM, Young RL, Blackshaw LA (2007) 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 500:863–875
Hunt J (2006) Exhaled breath condensate pH: reflecting acidification of the airway at all levels. Am J Respir Crit Care Med 173:366–367
Ikeda Y, Ueno A, Naraba H, Oh-ishi S (2001) Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice. Life Sci 69:2911–2919
Immke DC, McCleskey EW (2001) Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons. Nat Neurosci 4:869–870
Immke DC, McCleskey EW (2003) Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade. Neuron 37:75–84
Ishimaru Y, Inada H, Kubota M, Zhuang H, Tominaga M, Matsunami H (2006) Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci USA 103:12569–12574
Jahr H, van Driel M, van Osch GJ, Weinans H, van Leeuwen JP (2005) Identification of acid-sensing ion channels in bone. Biochem Biophys Res Commun 337:349–354
Jancsó N (1960) Role of the nerve terminals in the mechanism of inflammatory reactions. Bull Millard Fillmore Hosp 7:53–77
Jarvis MF, Burgard EC, McGaraughty S, Honore P, Lynch K, Brennan TJ, Subieta A, Van Biesen T, Cartmell J, Bianchi B, Niforatos W, Kage K, Yu H, Mikusa J, Wismer CT, Zhu CZ, Chu K, Lee CH, Stewart AO, Polakowski J, Cox BF, Kowaluk E, Williams M, Sullivan J, Faltynek C (2002) A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proc Natl Acad Sci USA 99:17179–17184
Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36:57–68
Jia Y, Lee LY (2007) Role of TRPV receptors in respiratory diseases. Biochim Biophys Acta 1772:915–927
Jiang M, Dun W, Tseng GN (1999) Mechanism for the effects of extracellular acidification on HERG-channel function. Am J Physiol 277:H1283–H1292
Jiang C, Rojas A, Wang R, Wang X (2005) CO2 central chemosensitivity: why are there so many sensing molecules? Respir Physiol Neurobiol 145:115–126
Jiang N, Rau KK, Johnson RD, Cooper BY (2006) Proton sensitivity Ca2+ permeability and molecular basis of acid-sensing ion channels expressed in glabrous and hairy skin afferents. J Neurophysiol 95:2466–2478
Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB (2004) Acid-induced pain and its modulation in humans. J Neurosci 24:10974–10979
Jordt SE, Tominaga M, Julius D (2000) Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc Natl Acad Sci USA 97:8134–8139
Kagawa S, Aoi M, Kubo Y, Kotani T, and Takeuchi K (2003) Stimulation by capsaicin of duodenal HCO3 − secretion via afferent neurons and vanilloid receptors in rats: comparison with acid-induced HCO3 − response. Dig Dis Sci 48:1850–1856
Kang D, Kim D (2004) Single-channel properties and pH sensitivity of two-pore domain K+ channels of the TALK family. Biochem Biophys Res Commun 315:836–844
Kang D, Kim D (2006) TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons. Am J Physiol 291:C138–C146
Kang JY, Yap I (1991) Acid and gastric ulcer pain. J Clin Gastroenterol 13:514–516
Kataoka S, Yang R, Ishimaru Y, Matsunami H, Sévigny J, Kinnamon JC, Finger TE (2008) The candidate sour taste receptor, PKD2L1, is expressed by type III taste cells in the mouse. Chem Senses 33:243–254
Kellenberger S, Schild L (2002) Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure. Physiol Rev 82:735–767
Kim Y, Bang H, Kim D (2000) TASK-3, a new member of the tandem pore K+ channel family. J Biol Chem 275:9340–9347
Kim Y, Gnatenco C, Bang H, Kim D (2001a) Localization of TREK-2 K+ channel domains that regulate channel kinetics and sensitivity to pressure, fatty acids and pHi. Pflügers Arch 442:952–960
Kim Y, Bang H, Gnatenco C, Kim D (2001b) Synergistic interaction and the role of C-terminus in the activation of TRAAK K+ channels by pressure, free fatty acids and alkali. Pflügers Arch 442:64–72
King BF, Townsend-Nicholson A, Wildman SS, Thomas T, Spyer KM, Burnstock G (2000) Coexpression of rat P2X2 and P2X6 subunits in Xenopus oocytes. J Neurosci 20:4871–4877
Kollarik M, Undem BJ (2002) Mechanisms of acid-induced activation of airway afferent nerve fibres in guinea-pig. J Physiol 543:591–600
Kollarik M, Fei Ru F, Undem BJ (2007) Acid-sensitive vagal sensory pathways and cough. Pulm Pharmacol Ther 20:402–411
Konnerth A, Lux HD, Morad M (1987) Proton-induced transformation of calcium channel in chick dorsal root ganglion cells. J Physiol (Lond) 386:603–633
Kress M, Waldmann R (2006) Acid sensing ionic channels. Curr Top Membr 57:241–276
Krishek BJ, Smart TG (2001) Proton sensitivity of rat cerebellar granule cell GABAA receptors: dependence on neuronal development. J Physiol (Lond) 530:219–233
Krishtal O (2003) The ASICs: signaling molecules? Modulators? Trends Neurosci 26:477–483
Krishtal OA, Pidoplichko VI (1981) A receptor for protons in the membrane of sensory neurons may participate in nociception. Neuroscience 6:2599–2601
Lamb K, Kang YM, Gebhart GF, Bielefeldt K (2003) Gastric inflammation triggers hypersensitivity to acid in awake rats. Gastroenterology 125:1410–1418
Leffler A, Mönter B, Koltzenburg M (2006) 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 139:699–709
Lehto SG, Tamir R, Deng H, Klionsky L, Kuang R, Le A, Lee D, Louis JC, Magal E, Manning BH, Rubino J, Surapaneni S, Tamayo N, Wang T, Wang J, Wang J, Wang W, Youngblood B, Zhang M, Zhu D, Norman MH, Gavva NR (2008) Antihyperalgesic effects of AMG8562, a novel vanilloid receptor TRPV1 modulator that does not cause hyperthermia in rats. J Pharmacol Exp Ther 326:218–229
Lesage F, Lazdunski M (2000) Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol 279:F793–F801
Lesage F, Terrenoire C, Romey G, Lazdunski M (2000) Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors. J Biol Chem 275:28398–28405
Leung SY, Niimi A, Williams AS, Nath P, Blanc FX, Dinh QT, Chung KF (2007) Inhibition of citric acid- and capsaicin-induced cough by novel TRPV-1 antagonist, V112220, in guinea-pig. Cough 3:10
Li C, Peoples RW, Weight FF (1996) Proton potentiation of ATP-gated ion channel responses to ATP and Zn2+ in rat nodose ganglion neurons. J Neurophysiol 76:3048–3058
Li C, Peoples RW, Weight FF (1997) Enhancement of ATP-activated current by protons in dorsal root ganglion neurons. Pflügers Arch 433:446–454
Li J, Maile MD, Sinoway AN, Sinoway LI (2004) Muscle pressor reflex: potential role of vanilloid type 1 receptor and acid-sensing ion channel. J Appl Physiol 97:1709–1714
Lin W, Burks CA, Hansen DR, Kinnamon SC, Gilbertson TA (2004) Taste receptor cells express pH-sensitive leak K+ channels. J Neurophysiol 92:2909–2919
Lingueglia E (2007) Acid-sensing ion channels in sensory perception. J Biol Chem 282:17325–17329
Lingueglia E, de Weille JR, Bassilana F, Heurteaux C, Sakai H, Waldmann R, Lazdunski M (1997) A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells. J Biol Chem 272:29778–29783
Liu L, Simon SA (1997) Capsazepine, a vanilloid receptor antagonist, inhibits nicotinic acetylcholine receptors in rat trigeminal ganglia. Neurosci Lett 228:29–32
Liu M, King BF, Dunn PM, Rong W, Townsend-Nicholson A, Burnstock G (2001) Coexpression of P2X3 and P2X2 receptor subunits in varying amounts generates heterogeneous populations of P2X receptors that evoke a spectrum of agonist responses comparable to that seen in sensory neurons. J Pharmacol Exp Ther 296:1043–1050
Liu M, Willmott NJ, Michael GJ, Priestley JV (2004) Differential pH and capsaicin responses of Griffonia simplicifolia IB4 (IB4)-positive and IB4-negative small sensory neurons. Neuroscience 127:659–672
Liu L, Hansen DR, Kim I, Gilbertson TA (2005) Expression and characterization of delayed rectifying K+ channels in anterior rat taste buds. Am J Physiol 289:C868–C880
Liu L, Mansfield KJ, Kristiana I, Vaux KJ, Millard RJ, Burcher E (2007) The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder. Neurourol Urodyn 26:433–438
LopezJimenez ND, Cavenagh MM, Sainz E, Cruz-Ithier MA, Battey JF, Sullivan SL (2006) Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. J Neurochem 98:68–77
López-López JR, Pérez-García MT (2007) An ASIC channel for acid chemotransduction. Circ Res 101:965–967
Lu YX, Owyang C (1999) Duodenal acid-induced gastric relaxation is mediated by multiple pathways. Am J Physiol 276:G1501–G1506
Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, Hofstetter H, Wolf RM, Seuwen K (2003) Proton-sensing G-protein-coupled receptors. Nature 425:93–98
Luger NM, Honore P, Sabino MA, Schwei MJ, Rogers SD, Mach DB, Clohisy DR, Mantyh PW (2001) Osteoprotegerin diminishes advanced bone cancer pain. Cancer Res 61:4038–4047
Lyall V, Alam RI, Malik SA, Phan TH, Vinnikova AK, Heck GL, DeSimone JA (2004) Basolateral Na+-H+ exchanger-1 in rat taste receptor cells is involved in neural adaptation to acidic stimuli. J Physiol (Lond) 556:159–173
Maingret F, Patel AJ, Lesage F, Lazdunski M, Honoré E (1999) Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J Biol Chem 274:26691–26696
Maingret F, Lauritzen I, Patel AJ, Heurteaux C, Reyes R, Lesage F, Lazdunski M, Honoré E (2000) TREK-1 is a heat-activated background K+ channel. EMBO J 19:2483–2491
Maingret F, Patel AJ, Lazdunski M, Honoré E (2001) The endocannabinoid anandamide is a direct and selective blocker of the background K+ channel TASK-1. EMBO J 20:47–54
Mamet J, Baron A, Lazdunski M, Voilley N (2002) Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. J Neurosci 22:10662–10670
Manela FD, Ren J, Gao J, McGuigan JE, Harty RF (1995) Calcitonin gene-related peptide modulates acid-mediated regulation of somatostatin and gastrin release from rat antrum. Gastroenterology 109:701–706
Mao J, Li L, McManus M, Wu J, Cui N, Jiang C (2002) Molecular determinants for activation of G-protein-coupled inward rectifier K+ (GIRK) channels by extracellular acidosis. J Biol Chem 277:46166–46171
Mathie A (2007) Neuronal two-pore-domain potassium channels and their regulation by G protein-coupled receptors. J Physiol (Lond) 578:377–385
Matthews PJ, Aziz Q, Facer P, Davis JB, Thompson DG, Anand P (2004) Increased capsaicin receptor TRPV1 nerve fibres in the inflamed human oesophagus. Eur J Gastroenterol Hepatol 16:897–902
Mazzuca M, Heurteaux C, Alloui A, Diochot S, Baron A, Voilley N, Blondeau N, Escoubas P, Gélot A, Cupo A, Zimmer A, Zimmer AM, Eschalier A, Lazdunski M (2007) A tarantula peptide against pain via ASIC1a channels and opioid mechanisms. Nat Neurosci 10:943–945
McLatchie LM, Bevan S (2001) The effects of pH on the interaction between capsaicin and the vanilloid receptor in rat dorsal root ganglia neurons. Br J Pharmacol 132:899–908
Meadows HJ, Randall AD (2001) Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel. Neuropharmacology 40:551–559
Medda BK, Sengupta JN, Lang IM, Shaker R (2005) Response properties of the brainstem neurons of the cat following intra-esophageal acid-pepsin infusion. Neuroscience 135:1285–1294
Medhurst AD, Rennie G, Chapman CG, Meadows H, Duckworth MD, Kelsell RE, Gloger II, Pangalos MN (2001) Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery. Mol Brain Res 86:101–114
Michael GJ, Priestley JV (1999) Differential expression of the mRNA for the vanilloid receptor subtype 1 in cells of the adult rat dorsal root and nodose ganglia and its downregulation by axotomy. J Neurosci 19:1844–1854
Miller P, Peers C, Kemp PJ (2004) Polymodal regulation of hTREK1 by pH, arachidonic acid, and hypoxia: physiological impact in acidosis and alkalosis. Am J Physiol 286:C272–C282
Miranda A, Nordstrom E, Mannem A, Smith C, Banerjee B, Sengupta JN (2007) The role of transient receptor potential vanilloid 1 in mechanical and chemical visceral hyperalgesia following experimental colitis. Neuroscience 148:1021–1032
Mistrík P, Torre V (2004) Histidine 518 in the S6-CNBD linker controls pH dependence and gating of HCN channel from sea-urchin sperm. Pflugers Arch 448:76–84
Mizuno A, Matsumoto N, Imai M, Suzuki M (2003) Impaired osmotic sensation in mice lacking TRPV4. Am J Physiol 285:C96–C101
Mogil JS, Breese NM, Witty MF, Ritchie J, Rainville ML, Ase A, Abbadi N, Stucky CL, Seguela P (2005) Transgenic expression of a dominant-negative ASIC3 subunit leads to increased sensitivity to mechanical and inflammatory stimuli. J Neurosci 25:9893–9901
Montrose MH, Akiba Y, Takeuchi K, Kaunitz JD (2006) Gastroduodenal mucosal defense. In: Johnson LR (ed) Physiology of the gastrointestinal tract, 4th edn. Academic, San Diego, pp 1259–1291
Morenilla-Palao C, Planells-Cases R, García-Sanz N, Ferrer-Montiel A (2004) Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J Biol Chem 279:25665–25672
Morton MJ, O'Connell AD, Sivaprasadarao A, Hunter M (2003) Determinants of pH sensing in the two-pore domain K+ channels TASK-1 and -2. Pflügers Arch 445:577–583
Morton MJ, Abohamed A, Sivaprasadarao A, Hunter M (2005) pH sensing in the two-pore domain K+ channel, TASK2. Proc Natl Acad Sci USA 102:16102–16106
Nagae M, Hiraga T, Wakabayashi H, Wang L, Iwata K, Yoneda T (2006) Osteoclasts play a part in pain due to the inflammation adjacent to bone. Bone 39:1107–1115
Nagae M, Hiraga T, Yoneda T (2007) Acidic microenvironment created by osteoclasts causes bone pain associated with tumor colonization. J Bone Miner Metab 25:99–104
Neelands TR, Jarvis MF, Han P, Faltynek CR, Surowy CS (2005) Acidification of rat TRPV1 alters the kinetics of capsaicin responses. Mol Pain 1:28
Newell K, Franchi A, Pouysségur J, Tannock I (1993) Studies with glycolysis-deficient cells suggest that production of lactic acid is not the only cause of tumor acidity. Proc Natl Acad Sci USA 90:1127–1131
Niemeyer MI, González-Nilo FD, Zúñiga L, González W, Cid LP, Sepúlveda FV (2007) Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel. Proc Natl Acad Sci USA 104:666–671
Nomura H, Turco AE, Pei Y, Kalaydjieva L, Schiavello T, Weremowicz S, Ji W, Morton CC, Meisler M, Reeders ST, Zhou J (1998) Identification of PKDL, a novel polycystic kidney disease 2-like gene whose murine homologue is deleted in mice with kidney and retinal defects. J Biol Chem 273:25967–25973
North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82:1013–1067
Nugent SG, Kumar D, Rampton DS, Evans DF (2001) Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs. Gut 48:71–577
Ohtori S, Inoue G, Koshi T, Ito T, Doya H, Saito T, Moriya H, Takahashi K (2006) Up-regulation of acid-sensing ion channel 3 in dorsal root ganglion neurons following application of nucleus pulposus on nerve root in rats. Spine 31:2048–2052
Ohtori S, Inoue G, Koshi T, Ito T, Watanabe T, Yamashita M, Yamauchi K, Suzuki M, Doya H, Moriya H, Takahashi Y, Takahashi K (2007) Sensory innervation of lumbar vertebral bodies in rats. Spine 32:1498–1502
Page AJ, Brierley SM, Martin CM, Price MP, Symonds E, Butler R, Wemmie JA, Blackshaw LA (2005) Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function. Gut 54:1408–1415
Page AJ, Brierley SM, Martin CM, Hughes PA, Blackshaw LA (2007) Acid sensing ion channels 2 and 3 are required for inhibition of visceral nociceptors by benzamil. Pain 133:150–160
Patapoutian A, Peier AM, Story GM, Viswanath V (2003) ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat Rev Neurosci 4:529–539
Patel AJ, Honoré E (2001) Properties and modulation of mammalian 2P domain K+ channels. Trends Neurosci 24:339–346
Patel AJ, Maingret F, Magnone V, Fosset M, Lazdunski M, Honoré E (2000) TWIK-2, an inactivating 2P domain K+ channel. J Biol Chem 275:28722–28730
Patterson LM, Zheng H, Ward SM, Berthoud HR (2003) Vanilloid receptor (VR1) expression in vagal afferent neurons innervating the gastrointestinal tract. Cell Tissue Res 311:277–287
Petersen M, LaMotte RH (1993) Effect of protons on the inward current evoked by capsaicin in isolated dorsal root ganglion cells. Pain 54:37–42
Petheo GL, Molnár Z, Róka A, Makara JK, Spät A (2001) A pH-sensitive chloride current in the chemoreceptor cell of rat carotid body. J Physiol (Lond) 535:95–106
Planells-Cases R, Garcìa-Sanz N, Morenilla-Palao C, Ferrer-Montiel A (2005) Functional aspects and mechanisms of TRPV1 involvement in neurogenic inflammation that leads to thermal hyperalgesia. Pflügers Arch 451:151–159
Poirot O, Vukicevic M, Boesch A, Kellenberger S (2004) Selective regulation of acid-sensing ion channel 1 by serine proteases. J Biol Chem 279:38448–38457
Poirot O, Berta T, Decosterd I, Kellenberger S (2006) Distinct ASIC currents are expressed in rat putative nociceptors and are modulated by nerve injury. J Physiol (Lond) 576:215–234
Price MP, McIlwrath SL, Xie J, Cheng C, Qiao J, Tarr DE, Sluka KA, Brennan TJ, Lewin GR, Welsh MJ (2001) The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. Neuron 32:1071–1083
Putnam RW, Filosa JA, Ritucci NA (2004) Cellular mechanisms involved in CO2 and acid signaling in chemosensitive neurons. Am J Physiol 287:C1493–C1526
Rajan S, Wischmeyer E, Xin Liu G, Preisig-Müller R, Daut J, Karschin A, Derst C (2000) TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histidine as pH sensor. J Biol Chem 275:16650–16657
Rajan S, Plant LD, Rabin ML, Butler MH, Goldstein SA (2005) Sumoylation silences the plasma membrane leak K+ channel K2P1. Cell 121:37–47
Rau KK, Cooper BY, Johnson RD (2006) Expression of TWIK-related acid sensitive K+ channels in capsaicin sensitive and insensitive cells of rat dorsal root ganglia. Neuroscience 141:955–963
Reeh PW, Kress M (2001) Molecular physiology of proton transduction in nociceptors. Curr Opin Pharmacol 1:45–51
Reyes R, Duprat F, Lesage F, Fink M, Salinas M, Farman N, Lazdunski M (1998) Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney. J Biol Chem 273:30863–30869
Reyes R, Lauritzen I, Lesage F, Ettaiche M, Fosset M, Lazdunski M (2000) Immunolocalization of the arachidonic acid and mechanosensitive baseline TRAAK potassium channel in the nervous system. Neuroscience 95:893–901
Ricciardolo FL, Gaston B, Hunt J (2004) Acid stress in the pathology of asthma. J Allergy Clin Immunol 113:610–619
Richter TA, Dvoryanchikov GA, Chaudhari N, Roper SD (2004a) Acid-sensitive two-pore domain potassium (K2P) channels in mouse taste buds. J Neurophysiol 92:1928–1936
Richter TA, Dvoryanchikov GA, Roper SD, Chaudhari N (2004b) Acid-sensing ion channel-2 is not necessary for sour taste in mice. J Neurosci 24:4088–4091
Rigoni M, Trevisani M, Gazzieri D, Nadaletto R, Tognetto M, Creminon C, Davis JB, Campi B, Amadesi S, Geppetti P, Harrison S (2003) Neurogenic responses mediated by vanilloid receptor-1 (TRPV1) are blocked by the high affinity antagonist, iodo-resiniferatoxin. Br J Pharmacol 138:977–985
Robinson DR, McNaughton PA, Evans ML, Hicks GA (2004) Characterization of the primary spinal afferent innervation of the mouse colon using retrograde labelling. Neurogastroenterol Motil 16:113–124
Rong W, Gourine AV, Cockayne DA, Xiang Z, Ford AP, Spyer KM, Burnstock G (2003) Pivotal role of nucleotide P2X2 receptor subunit of the ATP-gated ion channel mediating ventilatory responses to hypoxia. J Neurosci 23:11315–11321
Rong W, Hillsley K, Davis JB, Hicks G, Winchester WJ, Grundy D (2004) Jejunal afferent nerve sensitivity in wild-type and TRPV1 knockout mice. J Physiol (Lond) 560:867–881
Rukwied R, Chizh BA, Lorenz U, Obreja O, Margarit S, Schley M, Schmelz M (2007) Potentiation of nociceptive responses to low pH injections in humans by prostaglandin E2. J Pain 8:443–451
Ryu S, Liu B, Qin F (2003) Low pH potentiates both capsaicin binding and channel gating of VR1 receptors. J Gen Physiol 122:45–61
Ryu S, Liu B, Yao J, Fu Q, Qin F (2007) Uncoupling proton activation of vanilloid receptor TRPV1. J Neurosci 27:12797–12807
Sano Y, Inamura K, Miyake A, Mochizuki S, Kitada C, Yokoi H, Nozawa K, Okada H, Matsushime H, Furuichi K (2003) A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord. J Biol Chem 278:27406–27412
Schicho R, Schemann M, Pabst MA, Holzer P, Lippe IT (2003) Capsaicin-sensitive extrinsic afferents are involved in acid-induced activation of distinct myenteric neurons in the rat stomach. Neurogastroenterol Motil 15:33–44
Schicho R, Florian W, Liebmann I, Holzer P, Lippe IT (2004) Increased expression of TRPV1 receptor in dorsal root ganglia by acid insult of the rat gastric mucosa. Eur J Neurosci 19:1811–1818
Schmidt B, Hammer J, Holzer P, Hammer HF (2004) Chemical nociception in the jejunum induced by capsaicin. Gut 53:1109–1116
Schuligoi R, Jocic M, Heinemann A, Schöninkle E, Pabst MA, Holzer P (1998) Gastric acid-evoked c-fos messenger RNA expression in rat brainstem is signaled by capsaicin-resistant vagal afferents. Gastroenterology 115:649–660
Seabrook GR, Sutton KG, Jarolimek W, Hollingworth GJ, Teague S, Webb J, Clark N, Boyce S, Kerby J, Ali Z, Chou M, Middleton R, Kaczorowski G, Jones AB (2002) Functional properties of the high-affinity TRPV1 (VR1) vanilloid receptor antagonist (4-hydroxy-5-iodo-3-methoxyphenylacetate ester) iodo-resiniferatoxin. J Pharmacol Exp Ther 303:1052–1060
Semtner M, Schaefer M, Pinkenburg O, Plant TD (2007) Potentiation of TRPC5 by protons. J Biol Chem 282:33868–33878
Shimada S, Ueda T, Ishida Y, Yamamoto T, Ugawa S (2006) Acid-sensing ion channels in taste buds. Arch Histol Cytol 69:227–231
Shimokawa N, Dikic I, Sugama S, Koibuchi N (2005) Molecular responses to acidosis of central chemosensitive neurons in brain. Cell Signal 17:799–808
Shulkes A, Baldwin GS, Giraud AS (2006) Regulation of gastric acid secretion. In: Johnson LR (ed) Physiology of the gastrointestinal tract, 4th edn. Academic, San Diego, pp 1223–1258
Sluka KA, Price MP, Breese NA, Stucky CL, Wemmie JA, Welsh MJ (2003) Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain 106:229–239
Sluka KA, Radhakrishnan R, Benson CJ, Eshcol JO, Price MP, Babinski K, Audette KM, Yeomans DC, Wilson SP (2007) ASIC3 in muscle mediates mechanical, but not heat, hyperalgesia associated with muscle inflammation. Pain 129:102–112
Smith ES, Cadiou H, McNaughton PA (2007) Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action. Neuroscience 145:686–698
Somodi S, Varga Z, Hajdu P, Starkus JG, Levy DI, Gáspár R, Panyi G (2004) pH-dependent modulation of Kv1.3 inactivation: role of His399. Am J Physiol 287:C1067–C1076
Steen KH, Reeh PW (1993) Sustained graded pain and hyperalgesia from harmless experimental tissue acidosis in human skin. Neurosci Lett 154:113–116
Steen KH, Reeh PW, Anton F, Handwerker HO (1992) Protons selectively induce lasting excitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro. J Neurosci 12:86–95
Steen KH, Reeh PW, Kreysel HW (1995) Topical acetylsalicylic, salicylic acid and indomethacin suppress pain from experimental tissue acidosis in human skin. Pain 62:339–347
Stevens DR, Seifert R, Bufe B, Müller F, Kremmer E, Gauss R, Meyerhof W, Kaupp UB, Lindemann B (2001) Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli. Nature 413:631–635
Stoop R, Surprenant A, North RA (1997) Different sensitivities to pH of ATP-induced currents at four cloned P2X receptors. J Neurophysiol 78:1837–1840
Strecker T, Messlinger K, Weyand M, Reeh PW (2005) Role of different proton-sensitive channels in releasing calcitonin gene-related peptide from isolated hearts of mutant mice. Cardiovasc Res 65:405–410
Sugiura T, Dang K, Lamb K, Bielefeldt K, Gebhart GF (2005) Acid-sensing properties in rat gastric sensory neurons from normal and ulcerated stomach. J Neurosci 25:2617–2627
Sugiura T, Bielefeldt K, Gebhart GF (2007) Mouse colon sensory neurons detect extracellular acidosis via TRPV1. Am J Physiol 292:C1768–C1774
Surprenant A, Schneider DA, Wilson HL, Galligan JJ, North RA (2000) Functional properties of heteromeric P2X1/5 receptors expressed in HEK cells and excitatory junction potentials in guinea-pig submucosal arterioles. J Auton Nerv Syst 81:249–263
Sutherland SP, Benson CJ, Adelman JP, McCleskey EW (2001) Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons. Proc Natl Acad Aci USA 98:711–716
Suzuki M, Mizuno A, Kodaira K, Imai M (2003a) Impaired pressure sensation in mice lacking TRPV4. J Biol Chem 278:22664–22668
Suzuki M, Watanabe Y, Oyama Y, Mizuno A, Kusano E, Hirao A, Ookawara S (2003b) Localization of mechanosensitive channel TRPV4 in mouse skin. Neurosci Lett 353:189–192
Szallasi A, Blumberg PM (1999) Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 51:159–212
Szallasi A, Cortright DN, Blum CA, Eid SR (2007) The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept. Nat Rev Drug Discov 6:357–372
Szelényi Z, Hummel Z, Szolcsányi J, Davis JB (2004) Daily body temperature rhythm and heat tolerance in TRPV1 knockout and capsaicin pretreated mice. Eur J Neurosci 19:1421–1424
Talley EM, Solorzano G, Lei Q, Kim D, Bayliss DA (2001) CNS distribution of members of the two-pore-domain (KCNK) potassium channel family. J Neurosci 21:7491–7505
Tan ZY, Lu Y, Whiteis CA, Benson CJ, Chapleau MW, Abboud FM (2007) Acid-sensing ion channels contribute to transduction of extracellular acidosis in rat carotid body glomus cells. Circ Res 101:1009–1019
Tang L, Chen Y, Chen Z, Blumberg PM, Kozikowski AP, Wang ZJ (2007) Antinociceptive pharmacology of N-(4-chlorobenzyl)-N′-(4-hydroxy-3-iodo-5-methoxybenzyl) thiourea, a high-affinity competitive antagonist of the transient receptor potential vanilloid 1 receptor. J Pharmacol Exp Ther 321:791–798
Tashima K, Nakashima M, Kagawa S, Kato S, Takeuchi K (2002) Gastric hyperemic response induced by acid back-diffusion in rat stomachs following barrier disruption – relation to vanilloid type-1 receptors. Med Sci Monit 8:BR157–BR163
Tominaga M, Caterina M, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543
Tomura H, Mogi C, Sato K, Okajima F (2005) Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: a novel type of multi-functional receptors. Cell Signal 17:1466–1476
Trevisani M, Milan A, Gatti R, Zanasi A, Harrison S, Fontana G, Morice AH, Geppetti P (2004) Antitussive activity of iodo-resiniferatoxin in guinea pigs. Thorax 59:769–772
Uchiyama Y, Cheng CC, Danielson KG, Mochida J, Albert TJ, Shapiro IM, Risbud MV (2007) 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 22:1996–2006
Ugawa S, Ueda T, Ishida Y, Nishigaki M, Shibata Y, Shimada S (2002) Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors. J Clin Invest 110:1185–1190
Ugawa S, Yamamoto T, Ueda T, Ishida Y, Inagaki A, Nishigaki M, Shimada S (2003) Amiloride-insensitive currents of the acid-sensing ion channel-2a (ASIC2a)/ASIC2b heteromeric sour-taste receptor channel. J Neurosci 23:3616–3622
Ugawa S, Ueda T, Yamamura H, Shimada S (2005) In situ hybridization evidence for the coexistence of ASIC and TRPV1 within rat single sensory neurons. Mol Brain Res 136:125–133
Urban L, Campbell EA, Panesar M, Patel S, Chaudhry N, Kane S, Buchheit K, Sandells B, James IF (2000) In vivo pharmacology of SDZ 249-665, a novel, non-pungent capsaicin analogue. Pain 89:65–74
Van Buren JJ, Bhat S, Rotello R, Pauza ME, Premkumar LS (2005) Sensitization and translocation of TRPV1 by insulin and IGF-I. Mol Pain 1:17
Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49:6449–6465
Vellani V, Mapplebeck S, Moriondo A, Davis JB, McNaughton PA (2001) Protein kinase C activation potentiates gating of the vanilloid receptor VR1 by capsaicin, protons, heat and anandamide. J Physiol 534:813–825
Voilley N, de Weille J, Mamet J, Lazdunski M (2001) 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
Vulcu SD, Liewald JF, Gillen C, Rupp J, Nawrath H (2004) Proton conductance of human transient receptor potential-vanilloid type-1 expressed in oocytes of Xenopus laevis and in Chinese hamster ovary cells. Neuroscience 125:861–866
Wachter CH, Heinemann A, Donnerer J, Pabst MA, Holzer P (1998) Mediation by 5-hydroxytryptamine of the femoral vasoconstriction induced by acid challenge of the rat gastric mucosa. J Physiol (Lond) 509:541–550
Waldmann R (2001) Proton-gated cation channels – neuronal acid sensors in the central and peripheral nervous system. Adv Exp Med Biol 502:293–304
Waldmann R, Lazdunski M (1998) H+-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. Curr Opin Neurobiol 8:418–424
Waldmann R, Champigny G, Lingueglia E, De Weille JR, Heurteaux C, Lazdunski M (1999) H+-gated cation channels. Ann N Y Acad Sci 868:67–76
Wang L, Wang DH (2005) TRPV1 gene knockout impairs postischemic recovery in isolated perfused heart in mice. Circulation 112:3617–3623
Wang X, Wu J, Li L, Chen F, Wang R, Jiang C (2003) Hypercapnic acidosis activates KATP channels in vascular smooth muscles. Circ Res 92:1225–1232
Welch JM, Simon SA, Reinhart PH (2000) The activation mechanism of rat vanilloid receptor 1 by capsaicin involves the pore domain and differs from the activation by either acid or heat. Proc Natl Acad Sci USA 97:13889–13894
Welsh MJ, Price MP, Xie J (2002) Biochemical basis of touch perception: mechanosensory function of degenerin/epithelial Na+ channels. J Biol Chem 277:2369–2372
Wemmie JA, Price MP, Welsh MJ (2006) Acid-sensing ion channels: advances, questions and therapeutic opportunities. Trends Neurosci 29:578–586
Wildman SS, Brown SG, Rahman M, Noel CA, Churchill L, Burnstock G, Unwin RJ, King BF (2002) Sensitization by extracellular Ca2+ of rat P2X5 receptor and its pharmacological properties compared with rat P2X1. Mol Pharmacol 62:957–966
Woodbury CJ, Zwick M, Wang S, Lawson JJ, Caterina MJ, Koltzenburg M, Albers KM, Koerber HR, Davis BM (2004) Nociceptors lacking TRPV1 and TRPV2 have normal heat responses. J Neurosci 24:6410–6415
Wultsch T, Painsipp E, Shahbazian A, Mitrovic M, Edelsbrunner M, Waldmann R, Lazdunski M, Holzer P (2008) Deletion of the acid-sensing ion channel ASIC3 prevents gastritis-induced acid hyperresponsiveness of the stomach-brainstem axis. Pain 134:245–253
Wynn G, Ma B, Ruan HZ, Burnstock G (2004) Purinergic component of mechanosensory transduction is increased in a rat model of colitis. Am J Physiol 287:G647–G657
Xie J, Price MP, Berger AL, Welsh MJ (2002) DRASIC contributes to pH-gated currents in large dorsal root ganglion sensory neurons by forming heteromultimeric channels. J Neurophysiol 87:2835–2843
Xiong ZG, Chu XP, Simon RP (2006) Ca2+-permeable acid-sensing ion channels and ischemic brain injury. J Membr Biol 209:59–68
Xu GY, Huang LY (2002) Peripheral inflammation sensitizes P2X receptor-mediated responses in rat dorsal root ganglion neurons. J Neurosci 22:93–102
Xu GY, Winston JH, Shenoy M, Yin H, Pendyala S, Pasricha PJ (2007) Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis. Gastroenterology 133:1282–1292
Xu H, Cui N, Yang Z, Wu J, Giwa LR, Abdulkadir L, Sharma P, Jiang C (2001) Direct activation of cloned KATP channels by intracellular acidosis. J Biol Chem 276:12898–12902
Yagi J, Wenk HN, Naves LA, McCleskey EW (2006) Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia. Circ Res 99:501–509
Yang HYT, Tao T, Iadarola MJ (2008) Modulatory role of neuropeptide FF system in nociception and opiate analgesia. Neuropeptides 42:1–18
Yiangou Y, Facer P, Baecker PA, Ford AP, Knowles CH, Chan CL, Williams NS, Anand P (2001a) ATP-gated ion channel P2X3 is increased in human inflammatory bowel disease. Neurogastroenterol Motil 13:365–369
Yiangou Y, Facer P, Dyer NH, Chan CL, Knowles C, Williams NS, Anand P (2001b) Vanilloid receptor 1 immunoreactivity in inflamed human bowel. Lancet 357:1338–1339
Yiangou Y, Facer P, Smith JA, Sangameswaran L, Eglen R, Birch R, Knowles C, Williams N, Anand P (2001c) Increased acid-sensing ion channel ASIC-3 in inflamed human intestine. Eur J Gastroenterol Hepatol 13:891–896
Yuill K, Ashmole I, Stanfield PR (2004) The selectivity filter of the tandem pore potassium channel TASK-1 and its pH-sensitivity and ionic selectivity. Pflugers Arch 448:63–69
Yuill KH, Stansfeld PJ, Ashmole I, Sutcliffe MJ, Stanfield PR (2007) The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1: contributions of the pore domains. Pflugers Arch 455:333–348
Zeilhofer HU, Swandulla D, Reeh PW, Kress M (1996) Ca2+ permeability of the sustained proton-induced cation current in adult rat dorsal root ganglion neurons. J Neurophysiol 76:2834–2840
Zeilhofer HU, Kress M, Swandulla D (1997) Fractional Ca2+ currents through capsaicin- and proton-activated ion channels in rat dorsal root ganglion neurones. J Physiol (Lond) 503:67–78
Zhang M, Nurse CA (2004) CO2/pH chemosensory signaling in co-cultures of rat carotid body receptors and petrosal neurons: role of ATP and Ach. J Neurophysiol 92:3433–3445
Zhang X, Huang J, McNaughton PA (2005) NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 24:4211–4223
Zhong B, Wang DH (2007) TRPV1 gene knockout impairs preconditioning protection against myocardial injury in isolated perfused hearts in mice. Am J Physiol 293:H1791–H1798
Zhong Y, Dunn PM, Bardini M, Ford APDW, Cockayne DA, Burnstock G (2001) Changes in P2X receptor responses of sensory neurons from P2X3-deficient mice. Eur J Neurosci 14:1784–1792
Zong X, Stieber J, Ludwig A, Hofmann F, Biel M (2001) A single histidine residue determines the pH sensitivity of the pacemaker channel HCN2. J Biol Chem 276:6313–6319
Acknowledgements
Work performed in the author's laboratory was supported by the Zukunftsfonds Steiermark (grant 262), the Austrian Scientific Research Funds (FWF grant L25-B05), the Jubilee Foundation of the Austrian National Bank (grant 9858) and the Austrian Federal Ministry of Science and Research. Evelin Painsipp is acknowledged for drawing Fig. 2.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Holzer, P. (2009). Acid-Sensitive Ion Channels and Receptors. In: Canning, B., Spina, D. (eds) Sensory Nerves. Handbook of Experimental Pharmacology, vol 194. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79090-7_9
Download citation
DOI: https://doi.org/10.1007/978-3-540-79090-7_9
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-79089-1
Online ISBN: 978-3-540-79090-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)