Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

A proton-gated cation channel involved in acid-sensing

Abstract

Acid-sensing is associated with both nociception1 and taste transduction2. Stimulation of sensory neurons by acid is of particular interest, because acidosis accompanies many painful inflammatory and ischaemic conditions. The pain caused by acids is thought to be mediated by H+-gated cation channels present in sensory neurons3–5. We have now cloned a H+-gated channel (ASIC, for acid-sensing ionic channel) that belongs to the amilor-ide-sensitive Na+ channel6–1 Vdegenerin12–14 family of ion channels. Heterologous expression of ASIC induces an amiloride-sensitive cation (Na+ ≥ Ca2+ ≥ K+) channel which is transiently activated by rapid extracellular acidification. The biophysical and pharmacological properties of the ASIC channel closely match the H+-gated cation channel described in sensory neurons3,15,16. ASIC is expressed in dorsal root ganglia and is also distributed widely throughout the brain. ASIC appears to be the simplest of ligand-gated channels.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Rang, H. P., Bevan, S. & Dray, A. Chemical activation of nociceptive peripheral neurones. Br. Med. Bull. 47, 534–548 (1991).

    Article  CAS  Google Scholar 

  2. Lindemann, B. Taste reception. Physiol. Rev. 76, 718–766 (1996).

    Article  Google Scholar 

  3. Krishtal, O. A. & Pidoplichko, V. I. A receptor for protons in the membrane of sensory neurons may participate in nociception. Neurosdence 6, 2599–2601 (1981).

    Article  CAS  Google Scholar 

  4. Bevan, S. & Geppetti, P. Protons: small stimulants of capsaicin-sensitive sensory nerves. Trends Neurosci 17, 509–512 (1994).

    Article  CAS  Google Scholar 

  5. Akaike, N., Krishtal, O. A. & Maruyama, T. Proton-induced sodium current in frog isolated dorsal root ganglion ceils. J. Neurophysiol. 63, 805–813 (1990).

    Article  CAS  Google Scholar 

  6. Canessa, C. M., Horisberger, J. D. & Rossier, B. C. Epithelial sodium channel related to proteins involved in neurodegeneration. Nature 361, 467–470 (1993).

    Article  ADS  CAS  Google Scholar 

  7. Canessa, C. M. et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature 367, 463–467 (1994).

    Article  ADS  CAS  Google Scholar 

  8. Lingueglia, E., Voilley, N., Waldmann, R., Lazdunski, M. & Barby, P. Expression cloning of an epithelial amiloride-sensitive Na+ channel. A new channel type with homologies to Caenorhabditis elegans degenerins. FEBS Lett. 318, 95–99 (1993).

    Article  CAS  Google Scholar 

  9. Lingueglia, E. et al. Different homologous subunits of the amiloridc-sensitive Na+ channel are differently regulated by aldosterone. J. Biol. Chem. 269, 13736–13739 (1994).

    CAS  PubMed  Google Scholar 

  10. Lingueglia, E., Champigny, G., Lazdunski, M. & Barbry, P. Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel. Nature 378, 730–733 (1995).

    Article  ADS  CAS  Google Scholar 

  11. Waldmann, R., Champigny, G., Bassilana, F., Voilley, N. & Lazdunski, M. Molecular cloning and functional expression of a novel amiloride-sensitive Na channel. J. Biol. Chem. 270, 27411–27414 (1995).

    Article  CAS  Google Scholar 

  12. 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, 588–593 (1991).

    Article  ADS  CAS  Google Scholar 

  13. Huang, M. & Chalfie, M. Gene interactions affecting mechanosensory transduction in Caenorhabdits elegans. Nature 367, 467–470 (1994).

    Article  ADS  CAS  Google Scholar 

  14. Waldmann, R., Champigny, G., Voiiley, 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, 10433–10434 (1996).

    Article  CAS  Google Scholar 

  15. Kovalchuk Yu, N., Krishtal, O. A. & Nowycky, M. C. The proton-activated inward current of rat sensory neurons includes a calcium component. Neurosci. Lett. 115, 237–242 (1990).

    Article  Google Scholar 

  16. Konnerth, A., Lux, H. D. & Morad, M. Proton-induced transformation of calcium channel in chick dorsal root ganglion cells. J. Physiol. 386, 603–633 (1987).

    Article  CAS  Google Scholar 

  17. Davies, N. W., Lux, H. D. & Morad, M. Site and mechanism of activation of proton-induced sodium current in chick dorsal root ganglion neurones. J. Physiol. 400, 159–187 (1988).

    Article  CAS  Google Scholar 

  18. Korkushko, A. & Kryshtal, O. Blocking of proton-activated sodium permeability of the membranes of trigeminal ganglion neurons in the rat by organic cations. Neirofiziologiia 16, 557–561 (1984).

    CAS  PubMed  Google Scholar 

  19. Grantyn, R., Perouansky, M., Rodriguez-Tebar, A. & Lux, H. D. Expression of depolarizing voltage- and transmitter-activated currents in neuronal precursor cells from the rat brain is preceded by a proton-activated sodium current. Dev. Brain Res. 49, 150–155 (1989).

    Article  CAS  Google Scholar 

  20. Price, M. P., Snyder, P. M. & Welsh, M. J. Cloning and expression of a novel human brain Na channel. J. Biol. Chem. 271, 7879–7882 (1996).

    Article  CAS  Google Scholar 

  21. Akaike, N. & Ueno, S. Proton-induced current in neuronal cells. Prog. Neurobiol. 43, 73–83 (1994).

    Article  CAS  Google Scholar 

  22. Krishtal, O. A., Osipchuk, Y, V., Shelest, T. N. & Smirnoff, S. V. Rapid extracellular pH transients related to synaptic transmission in rat hippocampal slices. Brain Res. 436, 352–356 (1987).

    Article  CAS  Google Scholar 

  23. Chesler, M. & Kaila, K. Modulation ofpH by neuronal activity. Trends Neurosci. 15, 396–402 (1992).

    Article  CAS  Google Scholar 

  24. Bevan, S. & Yeats, J. Protons activate a cation conductance in a sub-population of rat dorsal root ganglion neurones. J. Physiol. 433, 145–161 (1991).

    Article  CAS  Google Scholar 

  25. Lewis, C. et al. Coexpression of P2X2and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Nature 377, 432–435 (1995).

    Article  ADS  CAS  Google Scholar 

  26. Barnard, E. A. The transmitter-gated channels: a range of receptor types and structures. Trends Pharmacol. Sci. 17, 305–309 (1996).

    Article  CAS  Google Scholar 

  27. Okada, Y., Miyamoto, T. & Sato, T. Activation of a cation conductance by acetic acid in taste cells isolated from the bullfrog. J. Exp. Biol. 187, 19–32 (1994).

    CAS  PubMed  Google Scholar 

  28. Liu, J., Schrank, B. & Waterson, R. Interaction between a putative mechanosensory membrane channel and a collagen. Science 273, 361–364 (1996).

    Article  ADS  CAS  Google Scholar 

  29. Waldmann, R., Champigny, G. & Lazdunski, M. Functional degenerin-containing chimeras identify residues essential for amiloride-sensitive Na+ channel function. J. Biol. Chem. 270, 11735–11737 (1995).

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Waldmann, R., Champigny, G., Bassilana, F. et al. A proton-gated cation channel involved in acid-sensing. Nature 386, 173–177 (1997). https://doi.org/10.1038/386173a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/386173a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing