Encyclopedia of Pain

2007 Edition

Acid-Sensing Ion Channels

  • Nicolas Voilley
  • Michel Lazdunski
Reference work entry
DOI: https://doi.org/10.1007/978-3-540-29805-2_35


ASIC; ASIC1a; brain sodium channel 2 (BNC2, BNaC2); ASIC1b: ASICβ; ASIC2a: mammalian degenerin 1 (MDEG1), brain sodium channel 1 (BNC1, BNaC1); ASIC2b: mammalian degenerin 2 (MDEG2); ASIC3: dorsal-root acid-sensing ion channel (DRASIC)


Acid-Sensing Ion Channels (ASICs) are membrane protein complexes that form depolarizing ion channels present on peripheral and/or central neurons. These channels are opened by extracellular protons. Their activation induces action potential triggering on neurons after an extracellular pH decrease to acidic values. Such tissue  acidosis occurs during  inflammation or  ischemia, and is a major source of pain.


ASICs are membrane protein complexes formed by four subunits among the six characterized isoforms (Fig. 1). The isoforms are coded by four different genes, two of them spliced in two variants: ASIC1a and ASIC1b, ASIC2a and ASIC2b, ASIC3 and ASIC4 (Chen et al. 1998; Garcia-Anoveros et al. 1997; Grunder et al. 2000;...

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  1. 1.
    Baron A, Deval E, Salinas M et al. (2002) Protein Kinase C Stimulates the Acid-Sensing Ion Channel ASIC2a Via the PDZ Domain-Containing Protein PICK1. J Biol Chem 277:50463–50468Google Scholar
  2. 2.
    Benson CJ, Xie J, Wemmie JA et al. (2002) Heteromultimers of DEG/ENaC Subunits Form H+-Gated Channels in Mouse Sensory Neurons. Proc Natl Acad Sci USA 99:2338–2343Google Scholar
  3. 3.
    Chen CC, England S, Akopian AN et al. (1998) A Sensory Neuron-Specific, Proton-Gated Ion Channel. Proc Natl Acad Sci USA 95:10240–10245Google Scholar
  4. 4.
    Chen CC, Zimmer A, Sun WH et al. (2002) A Role for ASIC3 in the Modulation of High-Intensity Pain Stimuli. Proc Natl Acad Sci USA 99:8992–8997Google Scholar
  5. 5.
    Escoubas P, De Weille JR, Lecoq A et al. (2000) Isolation of a Tarantula Toxin Specific for a Class of Proton-Gated Na+ Channels. J Biol Chem 275:25116–25121Google Scholar
  6. 6.
    Garcia-Anoveros J, Derfler B, Neville-Golden J et al. (1997) BNaC1 and BNaC2 Constitute a New Family of Human Neuronal Sodium Channels Related to Degenerins and Epithelial Sodium Channels. Proc Natl Acad Sci USA 94:1459–1464Google Scholar
  7. 7.
    Grunder S, Geissler HS, Bassler EL et al. (2000) A New Member of Acid-Sensing Ion Channels from Pituitary Gland. Neuroreport 11:1607–1611Google Scholar
  8. 8.
    Lingueglia E, Weille JR de, Bassilana F et al. (1997) A Modulatory Subunit of Acid Sensing Ion Channels in Brain and Dorsal Root Ganglion Cells. J Biol Chem 272:29778–29783Google Scholar
  9. 9.
    Mamet J, Baron A, Lazdunski M et al. (2002) Proinflammatory Mediators, Stimulators of Sensory Neuron Excitability Via the Expression of Acid-Sensing Ion Channels. J Neurosci 22:10662–10670Google Scholar
  10. 10.
    Mamet J, Lazdunski M, Voilley N (2003) How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons. J Biol Chem 278:48907–48913Google Scholar
  11. 11.
    Steen KH, Reeh PW, Kreysel HW (1996) Dose-Dependent Competitive Block by Topical Acetylsalicylic and Salicylic Acid of Low pH-Induced Cutaneous Pain. Pain 64:71–82Google Scholar
  12. 12.
    Sutherland SP, Benson CJ, Adelman JP et al. (2001) Acid-Sensing Ion Channel 3 Matches the Acid-Gated Current in Cardiac Ischemia-Sensing Neurons. Proc Natl Acad Sci USA 98:711–716Google Scholar
  13. 13.
    Voiley N (2004) Acid-sensing ion channels (ASICs): new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs). Curr Drug Targets Inflamm Allergy 3:71–79Google Scholar
  14. 14.
    Voilley N, de Weille J, Mamet J et al. (2001) Nonsteroid Anti-Inflammatory Drugs Inhibit Both the Activity and the Inflammation-Induced Expression of Acid-Sensing Ion Channels in Nociceptors. J Neurosci 21:8026–8033Google Scholar
  15. 15.
    Waldmann R, Bassilana F, de Weille J et al. (1997a) Molecular Cloning of a Non-Inactivating Proton-Gated Na+ Channel Specific for Sensory Neurons. J Biol Chem 272:20975–20978Google Scholar
  16. 16.
    Waldmann R, Champigny G, Bassilana F et al. (1997b) A Proton-Gated Cation Channel Involved in Acid-Sensing. Nature 386:173–177Google Scholar
  17. 17.
    Waldmann R, Lazdunski M (1998) H(+)-Gated Cation Channels: Neuronal Acid Sensors in the NaC/DEG Family of Ion Channels. Curr Opin Neurobiol 8:418–424Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • Nicolas Voilley
    • 1
  • Michel Lazdunski
    • 1
  1. 1.Institut de Pharmacologie Moleculaire et CellulaireValbonneFrance