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Gene Review

ASIC1  -  acid sensing (proton gated) ion channel 1

Homo sapiens

Synonyms: ACCN2, ASIC, 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

  • The ASIC genes encode proton-gated cation channels in both the central and peripheral nervous system that could be involved in pain transduction [6].
  • The biophysical and pharmacological properties of the ASIC channel closely match the H+-gated cation channel described in sensory neurons [7].
  • ASIC is expressed in dorsal root ganglia and is also distributed widely throughout the brain [7].
  • Specific blockade of NMDAR/CaMKII-ASIC coupling may reduce neuronal death after ischemia and other pathological conditions involving excessive glutamate release and acidosis [4].
  • Furthermore, NR2B-specific antagonist, CaMKII inhibitor, or overexpression of mutated form of ASIC1a with Ser478 or Ser479 replaced by alanine (ASIC1a-S478A, ASIC1a-S479A) in cultured hippocampal neurons prevented ischemia-induced enhancement of ASIC currents, cytoplasmic Ca(2+) elevation, as well as neuronal death [4].

Biological context of ACCN2

  • We have identified two new members of this superfamily (BNaC1 and BNaC2) in a human brain cDNA library [8].
  • Moreover, loss of ASIC impaired hippocampal long-term potentiation [9].
  • ASIC1 also showed significant phosphorylation under basal conditions [10].
  • Moreover, coexpression of ASIC and MDEG subunits in Xenopus oocytes generates an amiloride-sensitive H+-gated Na+ channel with novel properties (different kinetics, ionic selectivity, and pH sensitivity) [11].
  • When activated by acidification to pH 6.8 or 6.5, the probability of inducing action potentials correlated with the ASIC current density [12].

Anatomical context of ACCN2


Associations of ACCN2 with chemical compounds

  • The sensitivity to pH or amiloride of single versus co-expressed ASIC subunits was not significantly different; however, gadolinium ions inhibited ASIC3 and ASIC2a+3 responses with much higher potency (IC(50) approximately 40 microm) than the ASIC2a response (IC(50) >/=1 mm) [2].
  • In these cells, PCs induced an increase in [Ca2+]i that was inhibited by capsazepine, a TRPV1 antagonist, and/or by amiloride, an ASIC antagonist [17].
  • Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF [18].
  • Thus we examined the role played by purinergic receptors, vanilloid type 1 receptors (VR1), and acid-sensing ion channels (ASIC) in mediating H2PO4- -evoked pressor responses [19].
  • 0. At least some of this current is carried by ASICs because the current is increased by both Zn(2+), an ASIC modulator, and amiloride [20].

Other interactions of ACCN2

  • RESULTS: In the Western blot, there was a significant three-fold increase in the mean relative optical density of the ASIC-3 55-kDa band (but not ASIC-1 or ASIC-2) in full-thickness inflamed intestine, as well as in separated muscle and mucosal layers [1].
  • In addition, significant levels of ASIC1 and ASIC3 mRNA were found in skeletal muscle tissue samples [14].
  • Using heterologous expression of ASIC subunits in Xenopus oocytes, we show here that the biphasic response of heteromeric rat and human ASIC2A+3 subtypes to low pH is selectively modulated by the neuropeptide FF (NPFF) and by the related peptide FMRFamide [18].

Analytical, diagnostic and therapeutic context of ACCN2


  1. Increased acid-sensing ion channel ASIC-3 in inflamed human intestine. Yiangou, Y., Facer, P., Smith, J.A., Sangameswaran, L., Eglen, R., Birch, R., Knowles, C., Williams, N., Anand, P. European journal of gastroenterology & hepatology. (2001) [Pubmed]
  2. Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+. Babinski, K., Catarsi, S., Biagini, G., Séguéla, P. J. Biol. Chem. (2000) [Pubmed]
  3. Protein kinase C isoform antagonism controls BNaC2 (ASIC1) function. Berdiev, B.K., Xia, J., Jovov, B., Markert, J.M., Mapstone, T.B., Gillespie, G.Y., Fuller, C.M., Bubien, J.K., Benos, D.J. J. Biol. Chem. (2002) [Pubmed]
  4. Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death. Gao, J., Duan, B., Wang, D.G., Deng, X.H., Zhang, G.Y., Xu, L., Xu, T.L. Neuron (2005) [Pubmed]
  5. H(+)-gated cation channels. Waldmann, R., Champigny, G., Lingueglia, E., De Weille, J.R., Heurteaux, C., Lazdunski, M. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  6. Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure. Kellenberger, S., Schild, L. Physiol. Rev. (2002) [Pubmed]
  7. A proton-gated cation channel involved in acid-sensing. Waldmann, R., Champigny, G., Bassilana, F., Heurteaux, C., Lazdunski, M. Nature (1997) [Pubmed]
  8. BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels. García-Añoveros, J., Derfler, B., Neville-Golden, J., Hyman, B.T., Corey, D.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory. Wemmie, J.A., Chen, J., Askwith, C.C., Hruska-Hageman, A.M., Price, M.P., Nolan, B.C., Yoder, P.G., Lamani, E., Hoshi, T., Freeman, J.H., Welsh, M.J. Neuron (2002) [Pubmed]
  10. cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1. Leonard, A.S., Yermolaieva, O., Hruska-Hageman, A., Askwith, C.C., Price, M.P., Wemmie, J.A., Welsh, M.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  11. The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties. Bassilana, F., Champigny, G., Waldmann, R., de Weille, J.R., Heurteaux, C., Lazdunski, M. J. Biol. Chem. (1997) [Pubmed]
  12. Distinct ASIC currents are expressed in rat putative nociceptors and are modulated by nerve injury. Poirot, O., Berta, T., Decosterd, I., Kellenberger, S. J. Physiol. (Lond.) (2006) [Pubmed]
  13. Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. Alvarez de la Rosa, D., Zhang, P., Shao, D., White, F., Canessa, C.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  14. Functional properties and pharmacological inhibition of ASIC channels in the human SJ-RH30 skeletal muscle cell line. Gitterman, D.P., Wilson, J., Randall, A.D. J. Physiol. (Lond.) (2005) [Pubmed]
  15. Coexpression of Vanilloid Receptor Subtype-1 and Acid-sensing Ion Channel Genes in the Human Trigeminal Ganglion Neurons. Ugawa, S., Ueda, T., Yamamura, H., Nagao, M., Shimada, S. Chem. Senses (2005) [Pubmed]
  16. Malignant human gliomas express an amiloride-sensitive Na+ conductance. Bubien, J.K., Keeton, D.A., Fuller, C.M., Gillespie, G.Y., Reddy, A.T., Mapstone, T.B., Benos, D.J. Am. J. Physiol. (1999) [Pubmed]
  17. Vanilloid receptor activation by 2- and 10-microm particles induces responses leading to apoptosis in human airway epithelial cells. Agopyan, N., Bhatti, T., Yu, S., Simon, S.A. Toxicol. Appl. Pharmacol. (2003) [Pubmed]
  18. Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF. Catarsi, S., Babinski, K., Séguéla, P. Neuropharmacology (2001) [Pubmed]
  19. Vanilloid type 1 receptor and the acid-sensing ion channel mediate acid phosphate activation of muscle afferent nerves in rats. Gao, Z., Henig, O., Kehoe, V., Sinoway, L.I., Li, J. J. Appl. Physiol. (2006) [Pubmed]
  20. Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia. Yagi, J., Wenk, H.N., Naves, L.A., McCleskey, E.W. Circ. Res. (2006) [Pubmed]
  21. Acid-induced pain and its modulation in humans. Jones, N.G., Slater, R., Cadiou, H., McNaughton, P., McMahon, S.B. J. Neurosci. (2004) [Pubmed]
  22. Molecular cloning and characterization of human acid sensing ion channel (ASIC)2 gene promoter. Xia, J., Zhou, Z.H., Bubien, J.K., Fuller, C.M., Markert, J.M., Mapstone, T.B., Yancey Gillespie, G., Benos, D.J. Gene (2003) [Pubmed]
  23. Modulation of Acid-sensing Ion Channel Currents, Acid-induced Increase of Intracellular Ca2+, and Acidosis-mediated Neuronal Injury by Intracellular pH. Wang, W.Z., Chu, X.P., Li, M.H., Seeds, J., Simon, R.P., Xiong, Z.G. J. Biol. Chem. (2006) [Pubmed]
  24. An ASIC design for versatile receive front-end electronics of an ultrasonic medical imaging system--16 channel analog inputs and 4 dynamically focused beam outputs. Park, S.B., Kwak, J., Lee, K. Ultrasonic imaging. (2003) [Pubmed]
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