Letter

A proton-gated cation channel involved in acid-sensing

  • Nature volume 386, pages 173177 (13 March 1997)
  • doi:10.1038/386173a0
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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.

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References

  1. 1.

    , & Chemical activation of nociceptive peripheral neurones. Br. Med. Bull. 47, 534–548 (1991).

  2. 2.

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

  3. 3.

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

  4. 4.

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

  5. 5.

    , & Proton-induced sodium current in frog isolated dorsal root ganglion ceils. J. Neurophysiol. 63, 805–813 (1990).

  6. 6.

    , & Epithelial sodium channel related to proteins involved in neurodegeneration. Nature 361, 467–470 (1993).

  7. 7.

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

  8. 8.

    , , , & 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).

  9. 9.

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

  10. 10.

    , , & Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel. Nature 378, 730–733 (1995).

  11. 11.

    , , , & Molecular cloning and functional expression of a novel amiloride-sensitive Na channel. J. Biol. Chem. 270, 27411–27414 (1995).

  12. 12.

    & 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).

  13. 13.

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

  14. 14.

    , , , & The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans. J. Biol. Chem. 271, 10433–10434 (1996).

  15. 15.

    , & The proton-activated inward current of rat sensory neurons includes a calcium component. Neurosci. Lett. 115, 237–242 (1990).

  16. 16.

    , & Proton-induced transformation of calcium channel in chick dorsal root ganglion cells. J. Physiol. 386, 603–633 (1987).

  17. 17.

    , & Site and mechanism of activation of proton-induced sodium current in chick dorsal root ganglion neurones. J. Physiol. 400, 159–187 (1988).

  18. 18.

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

  19. 19.

    , , & 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).

  20. 20.

    , & Cloning and expression of a novel human brain Na channel. J. Biol. Chem. 271, 7879–7882 (1996).

  21. 21.

    & Proton-induced current in neuronal cells. Prog. Neurobiol. 43, 73–83 (1994).

  22. 22.

    , , & Rapid extracellular pH transients related to synaptic transmission in rat hippocampal slices. Brain Res. 436, 352–356 (1987).

  23. 23.

    & Modulation ofpH by neuronal activity. Trends Neurosci. 15, 396–402 (1992).

  24. 24.

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

  25. 25.

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

  26. 26.

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

  27. 27.

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

  28. 28.

    , & Interaction between a putative mechanosensory membrane channel and a collagen. Science 273, 361–364 (1996).

  29. 29.

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

  30. 30.

    , , , & Biochemical analysis of the membrane topology of the amiloride-sensitive Na+ channel. J. Biol. Chem. 269, 12981–12986 (1994).

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Author information

Author notes

    • Rainer Waldmann
    •  & Guy Champigny

    These authors contributed equally to this work

Affiliations

  1. Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, Valbonne 06560, France

    • Rainer Waldmann
    • , Guy Champigny
    • , Frédéric Bassilana
    • , Catherine Heurteaux
    •  & Michel Lazdunski

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