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Gene Review

Asic1  -  acid-sensing (proton-gated) ion channel 1

Rattus norvegicus

Synonyms: ASIC1, Accn2, Acid-sensing ion channel 1, Amiloride-sensitive cation channel 2, neuronal, BNaC2, ...
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Disease relevance of Accn2


High impact information on Accn2


Biological context of Accn2

  • Our results indicate that ASIC1b is an effective sensor of transient H(+) signals during slight acidosis and that, in addition to alternative splicing, interaction with di- and polyvalent cations extends the dynamic range of ASIC H(+) sensors [7].
  • A-317567 produced concentration-dependent inhibition of all pH 4.5-evoked ASIC currents with an IC50 ranging between 2 and 30muM, depending upon the type of ASIC current activated [9].
  • Klenow fragment-mediated labeling of DNA strand breaks determined that ASIC 2a induction did not occur in cells with detectable DNA damage [10].
  • Western blot analysis with an anti-ASIC 2a antibody revealed up-regulation of an 80 kD protein in ischemic rat brain [10].
  • Activation of the hippocampal ASIC-like current by a pH drop to 6.9 or 6.6 induces a transient depolarization which itself triggers an initial action potential (AP) followed by a sustained depolarization and trains of APs [11].

Anatomical context of Accn2


Associations of Accn2 with chemical compounds

  • Neuropeptide FF (NPFF) and FMRFamide have been shown to potentiate proton-gated currents from cultured sensory neurons and acid sensing ion channel (ASIC) cDNA transfected cells [14].
  • The EC50 and Hill coefficient for the activation of ASIC-like currents by protons are not affected by DTT [15].
  • Zn(2+) increases the acid sensitivity of ASIC channels, and consequently neuronal excitability [11].
  • We suggest that the pH dependence of the modulatory action of RFa-related peptides can be associated with the interaction of a positively charged arginine with histidine residues in the molecule of ASIC [16].
  • In decerebrate rats (n = 8), H+ evoked a pressor response that was not blocked by capsazepine but was attenuated by amiloride (an ASIC blocker) [17].

Regulatory relationships of Accn2

  • In particular, we examined the presence of ASIC1 in domains where the local pH may drop sufficiently to activate ASIC1 under physiological conditions [13].
  • Recently, others have shown that the neurotrophic factor NGF stimulates expression of acid-sensing ion channel molecules, which are members of the DEG/ENaC family [18].

Other interactions of Accn2


Analytical, diagnostic and therapeutic context of Accn2


  1. 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]
  2. Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Xiong, Z.G., Zhu, X.M., Chu, X.P., Minami, M., Hey, J., Wei, W.L., MacDonald, J.F., Wemmie, J.A., Price, M.P., Welsh, M.J., Simon, R.P. Cell (2004) [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. Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons. Immke, D.C., McCleskey, E.W. Nat. Neurosci. (2001) [Pubmed]
  5. 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]
  6. pH Dependency and desensitization kinetics of heterologously expressed combinations of acid-sensing ion channel subunits. Hesselager, M., Timmermann, D.B., Ahring, P.K. J. Biol. Chem. (2004) [Pubmed]
  7. Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1). Babini, E., Paukert, M., Geisler, H.S., Grunder, S. J. Biol. Chem. (2002) [Pubmed]
  8. Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels. Escoubas, P., De Weille, J.R., Lecoq, A., Diochot, S., Waldmann, R., Champigny, G., Moinier, D., Ménez, A., Lazdunski, M. J. Biol. Chem. (2000) [Pubmed]
  9. Electrophysiological and in vivo characterization of A-317567, a novel blocker of acid sensing ion channels. Dubé, G.R., Lehto, S.G., Breese, N.M., Baker, S.J., Wang, X., Matulenko, M.A., Honoré, P., Stewart, A.O., Moreland, R.B., Brioni, J.D. Pain (2005) [Pubmed]
  10. Global ischemia induces expression of acid-sensing ion channel 2a in rat brain. Johnson, M.B., Jin, K., Minami, M., Chen, D., Simon, R.P. J. Cereb. Blood Flow Metab. (2001) [Pubmed]
  11. ASIC-like, proton-activated currents in rat hippocampal neurons. Baron, A., Waldmann, R., Lazdunski, M. J. Physiol. (Lond.) (2002) [Pubmed]
  12. The extracellular domain determines the kinetics of desensitization in acid-sensitive ion channel 1. Coric, T., Zhang, P., Todorovic, N., Canessa, C.M. J. Biol. Chem. (2003) [Pubmed]
  13. Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system. Alvarez de la Rosa, D., Krueger, S.R., Kolar, A., Shao, D., Fitzsimonds, R.M., Canessa, C.M. J. Physiol. (Lond.) (2003) [Pubmed]
  14. 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]
  15. Acid sensing ionic channels: modulation by redox reagents. Andrey, F., Tsintsadze, T., Volkova, T., Lozovaya, N., Krishtal, O. Biochim. Biophys. Acta (2005) [Pubmed]
  16. Modulatory action of RFamide-related peptides on acid-sensing ionic channels is pH dependent: the role of arginine. Ostrovskaya, O., Moroz, L., Krishtal, O. J. Neurochem. (2004) [Pubmed]
  17. Muscle pressor reflex: potential role of vanilloid type 1 receptor and acid-sensing ion channel. Li, J., Maile, M.D., Sinoway, A.N., Sinoway, L.I. J. Appl. Physiol. (2004) [Pubmed]
  18. ENaC proteins are required for NGF-induced neurite growth. Drummond, H.A., Furtado, M.M., Myers, S., Grifoni, S., Parker, K.A., Hoover, A., Stec, D.E. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  19. 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]
  20. In situ hybridization evidence for the coexistence of ASIC and TRPV1 within rat single sensory neurons. Ugawa, S., Ueda, T., Yamamura, H., Shimada, S. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  21. Acidic stimuli activates two distinct pathways in taste receptor cells from rat fungiform papillae. Liu, L., Simon, S.A. Brain Res. (2001) [Pubmed]
  22. An acid sensing ion channel (ASIC) localizes to small primary afferent neurons in rats. Olson, T.H., Riedl, M.S., Vulchanova, L., Ortiz-Gonzalez, X.R., Elde, R. Neuroreport (1998) [Pubmed]
  23. Two types of acid-sensing ion channel currents in rat hippocampal neurons. Weng, X.C., Zheng, J.Q., Gai, X.D., Li, J., Xiao, W.B. Neurosci. Res. (2004) [Pubmed]
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