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

Mus musculus

Synonyms: AI843610, ASIC, ASIC1, ASIC1 beta, ASIC1a, ...
 
 
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Disease relevance of Accn2

  • In focal ischemia, intracerebroventricular injection of ASIC1a blockers or knockout of the ASIC1a gene protects the brain from ischemic injury and does so more potently than glutamate antagonism [1].
  • In contrast, ASIC1 knockouts develop hyperalgesia similar to their wildtype littermates [2].
  • ASIC3 and ASIC1 mediate FMRFamide-related peptide enhancement of H+-gated currents in cultured dorsal root ganglion neurons [3].
  • We found that extracellular acidosis elicited a greater current density in amygdala neurons than hippocampal neurons and that disrupting the ASIC1 gene eliminated H+-evoked currents in the amygdala [4].
  • These findings further suggest that ASIC1a is a novel molecular target involved in ischaemic brain injury [5].
  • Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone [6].
 

Psychiatry related information on Accn2

  • These data raise the possibility that ASIC1a and H(+)-gated currents may contribute to the development of abnormal fear and to anxiety disorders in humans [7].
 

High impact information on Accn2

  • Cells lacking endogenous ASICs are resistant to acid injury, while transfection of Ca2+ -permeable ASIC1a establishes sensitivity [1].
  • CONCLUSIONS: ASIC1 influences visceral but not cutaneous mechanoreceptor function, suggesting that different mechanisms underlie mechanosensory function in gut and skin [8].
  • The role of ASIC1 is highlighted by prolonging gastric emptying of a meal in ASIC1-/- animals [8].
  • RESULTS: ASIC1 was expressed in sensory ganglia and was lost after disruption of the ASIC1 gene [8].
  • The results show that acid-sensitive channels are expressed in midbrain dopamine neurons and suggest that ammonium sensitivity is a widely distributed ASIC characteristic in the CNS, including the hippocampus [9].
 

Chemical compound and disease context of Accn2

 

Biological context of Accn2

 

Anatomical context of Accn2

  • Here they investigate further ASIC1a in gut mechanoreceptors, and compare its influence with ASIC2 and ASIC3 [14].
  • METHODS AND RESULTS: Expression of ASIC1a, 2, and 3 mRNA was found in vagal (nodose) and dorsal root ganglia (DRG), and was lost in mice lacking the respective genes [14].
  • These findings contrast sharply with the effects of ASIC1, 2, and 3 in skin, suggesting that targeting these subunits with pharmacological agents may have different and more pronounced effects on mechanosensitivity in the viscera [14].
  • Localization and comparative analysis of acid-sensing ion channel (ASIC1, 2, and 3) mRNA expression in mouse colonic sensory neurons within thoracolumbar dorsal root ganglia [15].
  • The acid-sensing ion channel 1a (ASIC1a) is abundantly expressed in the amygdala complex and other brain regions associated with fear [7].
 

Associations of Accn2 with chemical compounds

  • These data demonstrate that p11, already known to traffic members of the voltage-gated sodium and potassium channel families as well as transient receptor potential and chloride channels, also plays a selective role in enhancing ASIC1a functional expression [11].
  • We have recently demonstrated that ASIC function is regulated by serine proteases [16].
  • Ca(2+) permeability of ASIC1a is low, whereas ASIC1b is impermeable to Ca(2+) [12].
  • Site-directed mutagenesis studies identified involvement of cysteine 61 and lysine 133, located in the extracellular domain of the ASIC1a subunit, in the modulation of ASICs by oxidizing and reducing agents, respectively [17].
  • Modulation of Acid-sensing Ion Channel Currents, Acid-induced Increase of Intracellular Ca2+, and Acidosis-mediated Neuronal Injury by Intracellular pH [18].
 

Other interactions of Accn2

 

Analytical, diagnostic and therapeutic context of Accn2

References

  1. 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]
  2. Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Sluka, K.A., Price, M.P., Breese, N.M., Stucky, C.L., Wemmie, J.A., Welsh, M.J. Pain (2003) [Pubmed]
  3. ASIC3 and ASIC1 mediate FMRFamide-related peptide enhancement of H+-gated currents in cultured dorsal root ganglion neurons. Xie, J., Price, M.P., Wemmie, J.A., Askwith, C.C., Welsh, M.J. J. Neurophysiol. (2003) [Pubmed]
  4. Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning. Wemmie, J.A., Askwith, C.C., Lamani, E., Cassell, M.D., Freeman, J.H., Welsh, M.J. J. Neurosci. (2003) [Pubmed]
  5. Prolonged activation of ASIC1a and the time window for neuroprotection in cerebral ischaemia. Pignataro, G., Simon, R.P., Xiong, Z.G. Brain (2007) [Pubmed]
  6. Seizure termination by acidosis depends on ASIC1a. Ziemann, A.E., Schnizler, M.K., Albert, G.W., Severson, M.A., Howard, M.A., Welsh, M.J., Wemmie, J.A. Nat. Neurosci. (2008) [Pubmed]
  7. Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior. Wemmie, J.A., Coryell, M.W., Askwith, C.C., Lamani, E., Leonard, A.S., Sigmund, C.D., Welsh, M.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function. Page, A.J., Brierley, S.M., Martin, C.M., Martinez-Salgado, C., Wemmie, J.A., Brennan, T.J., Symonds, E., Omari, T., Lewin, G.R., Welsh, M.J., Blackshaw, L.A. Gastroenterology (2004) [Pubmed]
  9. Acid-sensitive ionic channels in midbrain dopamine neurons are sensitive to ammonium, which may contribute to hyperammonemia damage. Pidoplichko, V.I., Dani, J.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  10. The role of the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) in proton sensitivity of subpopulations of primary nociceptive neurons in rats and mice. Leffler, A., Mönter, B., Koltzenburg, M. Neuroscience (2006) [Pubmed]
  11. Annexin II light chain p11 promotes functional expression of acid-sensing ion channel ASIC1a. Donier, E., Rugiero, F., Okuse, K., Wood, J.N. J. Biol. Chem. (2005) [Pubmed]
  12. Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b. Bässler, E.L., Ngo-Anh, T.J., Geisler, H.S., Ruppersberg, J.P., Gründer, S. J. Biol. Chem. (2001) [Pubmed]
  13. Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord. Wu, L.J., Duan, B., Mei, Y.D., Gao, J., Chen, J.G., Zhuo, M., Xu, L., Wu, M., Xu, T.L. J. Biol. Chem. (2004) [Pubmed]
  14. Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function. Page, A.J., Brierley, S.M., Martin, C.M., Price, M.P., Symonds, E., Butler, R., Wemmie, J.A., Blackshaw, L.A. Gut (2005) [Pubmed]
  15. Localization and comparative analysis of acid-sensing ion channel (ASIC1, 2, and 3) mRNA expression in mouse colonic sensory neurons within thoracolumbar dorsal root ganglia. Hughes, P.A., Brierley, S.M., Young, R.L., Blackshaw, L.A. J. Comp. Neurol. (2007) [Pubmed]
  16. Trypsin cleaves acid-sensing ion channel 1a in a domain that is critical for channel gating. Vukicevic, M., Weder, G., Boillat, A., Boesch, A., Kellenberger, S. J. Biol. Chem. (2006) [Pubmed]
  17. ASIC1a-specific modulation of acid-sensing ion channels in mouse cortical neurons by redox reagents. Chu, X.P., Close, N., Saugstad, J.A., Xiong, Z.G. J. Neurosci. (2006) [Pubmed]
  18. 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]
  19. Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons. Askwith, C.C., Wemmie, J.A., Price, M.P., Rokhlina, T., Welsh, M.J. J. Biol. Chem. (2004) [Pubmed]
 
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