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Gene Review

Asic3  -  acid-sensing (proton-gated) ion channel 3

Rattus norvegicus

Synonyms: ASIC3, Accn3, Acid-sensing ion channel 3, Amiloride-sensitive cation channel 3, DRASIC, ...
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Disease relevance of Accn3


High impact information on Accn3

  • We report that H(+) opens ASIC3 by speeding release of Ca(2+) from a high-affinity binding site (K(Ca) = 150 nM) on the extracellular side of the pore [4].
  • The ASIC3-like current in primary cultured sensory neurons is partly and reversibly inhibited by APETx2 with an IC50 of 216 nM, probably due to the mixed inhibitions of various co-expressed ASIC3-containing channels [5].
  • Here we show that acid-sensing ion channel 3 (ASIC3), but no other known acid-sensing ion channel, reproduces the functional features of the channel that underlies the large acid-evoked current in cardiac afferents [6].
  • ASIC3 and the native channel are both especially sensitive to pH, interact similarly with Ca(2+), and gate rapidly between closed, open, and desensitized states [6].
  • NGF acts through AP1 response elements in ASIC3 encoding gene promoter [2].

Biological context of Accn3

  • However, it can associate both with MDEG1 and another recently cloned H+-activated channel DRASIC to form heteropolymers which display different kinetics, pH dependences, and ion selectivities [7].
  • Up-regulation of acid-sensing ion channel 3 in dorsal root ganglion neurons following application of nucleus pulposus on nerve root in rats [8].

Anatomical context of Accn3


Associations of Accn3 with chemical compounds

  • In this study, we report that another mammalian peptide neuropeptide SF (NPSF), derived from the same precursor, also considerably increases the amplitude of the sustained current of heterologously expressed ASIC3 (12-fold vs. 19- and nine-fold for FMRFamide and NPFF, respectively) with an EC(50) of approximately 50 microM [12].
  • Finally, the effect of lidocaine on pain and ASIC3 expression in the disc herniation model was examined [8].

Other interactions of Accn3


Analytical, diagnostic and therapeutic context of Accn3


  1. ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1. Deval, E., Salinas, M., Baron, A., Lingueglia, E., Lazdunski, M. J. Biol. Chem. (2004) [Pubmed]
  2. How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons. Mamet, J., Lazdunski, M., Voilley, N. J. Biol. Chem. (2003) [Pubmed]
  3. Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. Mamet, J., Baron, A., Lazdunski, M., Voilley, N. J. Neurosci. (2002) [Pubmed]
  4. Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade. Immke, D.C., McCleskey, E.W. Neuron (2003) [Pubmed]
  5. A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. Diochot, S., Baron, A., Rash, L.D., Deval, E., Escoubas, P., Scarzello, S., Salinas, M., Lazdunski, M. EMBO J. (2004) [Pubmed]
  6. Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons. Sutherland, S.P., Benson, C.J., Adelman, J.P., McCleskey, E.W. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  7. A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells. Lingueglia, E., de Weille, J.R., Bassilana, F., Heurteaux, C., Sakai, H., Waldmann, R., Lazdunski, M. J. Biol. Chem. (1997) [Pubmed]
  8. Up-regulation of acid-sensing ion channel 3 in dorsal root ganglion neurons following application of nucleus pulposus on nerve root in rats. Ohtori, S., Inoue, G., Koshi, T., Ito, T., Doya, H., Saito, T., Moriya, H., Takahashi, K. Spine (2006) [Pubmed]
  9. A sensory neuron-specific, proton-gated ion channel. Chen, C.C., England, S., Akopian, A.N., Wood, J.N. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  10. Single channel properties of rat acid-sensitive ion channel-1alpha, -2a, and -3 expressed in Xenopus oocytes. Zhang, P., Canessa, C.M. J. Gen. Physiol. (2002) [Pubmed]
  11. Increased expression of TRPV1 receptor in dorsal root ganglia by acid insult of the rat gastric mucosa. Schicho, R., Florian, W., Liebmann, I., Holzer, P., Lippe, I.T. Eur. J. Neurosci. (2004) [Pubmed]
  12. Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability. Deval, E., Baron, A., Lingueglia, E., Mazarguil, H., Zajac, J.M., Lazdunski, M. Neuropharmacology (2003) [Pubmed]
  13. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels. Groth, M., Helbig, T., Grau, V., Kummer, W., Haberberger, R.V. Respir. Res. (2006) [Pubmed]
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