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ASIC1

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 684

Nomenclature: ASIC1

Family: Acid-sensing (proton-gated) ion channels (ASICs)

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 528 12q13.12 ASIC1 acid sensing ion channel subunit 1
Mouse 2 526 15 F1 Asic1 acid-sensing (proton-gated) ion channel 1
Rat 2 526 7q36 Asic1 acid sensing ion channel subunit 1
Previous and Unofficial Names Click here for help
BNaC2 | ACCN2 | amiloride-sensitive cation channel 2, neuronal | acid-sensing ion channel 1 | brain sodium channel 2 | ASIC1 beta | ASICalpha | acid-sensing (proton-gated) ion channel 1 | acid sensing (proton gated) ion channel 1
Database Links Click here for help
ChEMBL Target CHEMBL1628477 (Hs), CHEMBL3232694 (Mm), CHEMBL3562170 (Rn)
DrugBank Target P78348 (Hs)
Ensembl Gene ENSG00000110881 (Hs), ENSMUSG00000023017 (Mm), ENSRNOG00000018789 (Rn)
Entrez Gene 41 (Hs), 11419 (Mm), 79123 (Rn)
Human Protein Atlas ENSG00000110881 (Hs)
KEGG Gene hsa:41 (Hs), mmu:11419 (Mm), rno:79123 (Rn)
OMIM 602866 (Hs)
Pharos P78348 (Hs)
UniProtKB P78348 (Hs), Q6NXK8 (Mm), P55926 (Rn)
Wikipedia ASIC1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of chicken (Gallus gallus) ASIC1a with Texas coral snake toxin (MitTx).
PDB Id:  4NTW
Resolution:  2.07Å
Species:  Chicken
References:  1
Image of receptor 3D structure from RCSB PDB
Description:  Structure of an acid sensing ion channel in a resting state with barium
PDB Id:  5WKU
Resolution:  2.95Å
Species:  Chicken
References:  22
Functional Characteristics Click here for help
ASIC1a: γ =14pS
PNa/PK = 5-13, PNa/PCa =2.5
rapid activation rate (5.8-13.7 ms), rapid inactivation rate (1.2-4 s) @ pH 6.0, slow recovery (5.3-13s) @ pH 7.4
ASIC1b: γ =19 pS
PNa/PK =14.0, PNa >> PCa
rapid activation rate (9.9 ms), rapid inactivation rate (0.9-1.7 s) @ pH 6.0, slow recovery (4.4-7.7 s) @ pH 7.4
Natural/Endogenous Ligands Click here for help
H+

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Activators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
Extracellular H+ Click here for species-specific activity table Ligand is endogenous in the given species Hs - ~5.1 – 6.8 pEC50 - no
⤷ pEC50 ~6.2 – 6.8 (EC50 ~6.3x10-7 – 1.6x10-7 M) ASIC1a
Not voltage dependent
pEC50 ~5.1 – 6.2 (EC50 ~8x10-6 – 6.3x10-7 M) ASIC1b
Not voltage dependent
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
Pi-hexatoxin-Hi1a Peptide Hs - no ~9.3 pIC50 - no 4
⤷ pIC50 ~9.3 ASIC1a [4]
Not voltage dependent
psalmotoxin 1 Peptide Hs - no 9.0 pIC50 - no 10
⤷ pIC50 9.0 (IC50 9x10-10 M) ASIC1a [10]
Not voltage dependent
Pi-theraphotoxin-Hm3a Peptide Hs - no ~8.5 pIC50 - no 9
⤷ pIC50 ~8.5 ASIC1a [9]
Not voltage dependent
Zn2+ Click here for species-specific activity table Hs - no ~8.2 pIC50 - no 5
⤷ pIC50 ~8.2 (IC50 ~7x10-9 M) ASIC1a [5]
Not voltage dependent
mambalgin-1 Peptide Hs - no ~7.0 – 7.3 pIC50 - no 2,7
⤷ pIC50 ~7.3 ASIC1a [7]
Not voltage dependent
pIC50 ~7.0 ASIC1b [2]
Not voltage dependent
diminazene Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs - no ~6.5 pIC50 - no 11-12,16
⤷ pIC50 ~6.5 ASIC1a & ASIC1b [11-12,16]
Not voltage dependent
A-317567 Small molecule or natural product Rn - no ~5.7 pIC50 - no 8
⤷ pIC50 ~5.7 (IC50 ~2x10-6 M) ASIC1a [8]
Not voltage dependent
Pb2+ Click here for species-specific activity table Hs - no ~5.4 – 5.8 pIC50 - no 21
⤷ pIC50 ~5.8 (IC50 ~1.5x10-6 M) ASIC1b
Not voltage dependent
pIC50 ~5.4 (IC50 ~4x10-6 M) ASIC1a [21]
Not voltage dependent
benzamil Small molecule or natural product Click here for species-specific activity table Hs - no 5.0 pIC50 - no 20
⤷ pIC50 5.0 (IC50 1x10-5 M) ASIC1a [20]
Not voltage dependent
ethylisopropylamiloride Small molecule or natural product Click here for species-specific activity table Hs - no 5.0 pIC50 - no 20
⤷ pIC50 5.0 (IC50 1x10-5 M) ASIC1a [20]
Not voltage dependent
nafamostat Small molecule or natural product Approved drug Click here for species-specific activity table Hs - no ~4.9 pIC50 - no 18
⤷ pIC50 ~4.9 (IC50 ~1.3x10-5 M) ASIC1a [18]
Not voltage dependent
amiloride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - no 4.6 – 5.0 pIC50 - no 20
⤷ pIC50 5.0 (IC50 1x10-5 M) ASIC1a
Not voltage dependent
pIC50 4.6 – 4.7 (IC50 2.3x10-5 – 2.1x10-5 M) ASIC1b [20]
Not voltage dependent
ibuprofen Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs - no ~3.5 pIC50 - no 13,19
⤷ pIC50 ~3.5 (IC50 ~3.5x10-4 M) ASIC1a [13,19]
Not voltage dependent
flurbiprofen Small molecule or natural product Approved drug Immunopharmacology Ligand Rn - no 3.5 pIC50 - no 19
⤷ pIC50 3.5 (IC50 3.5x10-4 M) ASIC1a [19]
Not voltage dependent
View species-specific channel blocker tables
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]psalmotoxin 1 Peptide Ligand is labelled Ligand is radioactive Hs - 9.7 pKd 15
⤷ pKd 9.7 (Kd 2.13x10-10 M) ASIC1a [15]
Immunopharmacology Comments
Non-steroidal anti-inflammatory drugs (NSAIDs) are direct inhibitors of ASIC currents (reviewed in [3]). Inflammatory conditions and particular pro-inflammatory mediators such as arachidonic acid induce overexpression of ASIC-encoding genes and enhance ASIC currents [6,14,17]. The sustained current component mediated by ASIC3 is potentiated by hypertonic solutions in a manner that is synergistic with the effect of arachidonic acid [6].

References

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1. Baconguis I, Bohlen CJ, Goehring A, Julius D, Gouaux E. (2014) X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel. Cell, 156 (4): 717-29. [PMID:24507937]

2. Baron A, Diochot S, Salinas M, Deval E, Noël J, Lingueglia E. (2013) Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels. Toxicon, 75: 187-204. [PMID:23624383]

3. Baron A, Lingueglia E. (2015) Pharmacology of acid-sensing ion channels - Physiological and therapeutical perspectives. Neuropharmacology, 94: 19-35. [PMID:25613302]

4. Brunner FS, Anaya-Rojas JM, Matthews B, Eizaguirre C. (2017) Experimental evidence that parasites drive eco-evolutionary feedbacks. Proc. Natl. Acad. Sci. U.S.A., 114 (14): 3678-3683. [PMID:28320947]

5. Chu XP, Wemmie JA, Wang WZ, Zhu XM, Saugstad JA, Price MP, Simon RP, Xiong ZG. (2004) Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels. J. Neurosci., 24 (40): 8678-89. [PMID:15470133]

6. Deval E, Noël J, Lay N, Alloui A, Diochot S, Friend V, Jodar M, Lazdunski M, Lingueglia E. (2008) ASIC3, a sensor of acidic and primary inflammatory pain. EMBO J., 27 (22): 3047-55. [PMID:18923424]

7. Diochot S, Baron A, Salinas M, Douguet D, Scarzello S, Dabert-Gay AS, Debayle D, Friend V, Alloui A, Lazdunski M et al.. (2012) Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature, 490 (7421): 552-5. [PMID:23034652]

8. Dubé GR, Lehto SG, Breese NM, Baker SJ, Wang X, Matulenko MA, Honoré P, Stewart AO, Moreland RB, Brioni JD. (2005) Electrophysiological and in vivo characterization of A-317567, a novel blocker of acid sensing ion channels. Pain, 117 (1-2): 88-96. [PMID:16061325]

9. Er SY, Cristofori-Armstrong B, Escoubas P, Rash LD. (2017) Discovery and molecular interaction studies of a highly stable, tarantula peptide modulator of acid-sensing ion channel 1. Neuropharmacology, 127: 185-195. [PMID:28327374]

10. Escoubas P, De Weille JR, Lecoq A, Diochot S, Waldmann R, Champigny G, Moinier D, Ménez A, Lazdunski M. (2000) Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels. J. Biol. Chem., 275 (33): 25116-21. [PMID:10829030]

11. Krauson AJ, Rooney JG, Carattino MD. (2018) Molecular basis of inhibition of acid sensing ion channel 1A by diminazene. PLoS One, 13 (5): e0196894. [PMID:29782492]

12. Lee JYP, Saez NJ, Cristofori-Armstrong B, Anangi R, King GF, Smith MT, Rash LD. (2018) Inhibition of acid-sensing ion channels by diminazene and APETx2 evoke partial and highly variable antihyperalgesia in a rat model of inflammatory pain. Br. J. Pharmacol., 175 (12): 2204-2218. [PMID:29134638]

13. Lynagh T, Romero-Rojo JL, Lund C, Pless SA. (2017) Molecular Basis for Allosteric Inhibition of Acid-Sensing Ion Channel 1a by Ibuprofen. J Med Chem, 60 (19): 8192-8200. [PMID:28949138]

14. Mamet J, Baron A, Lazdunski M, Voilley N. (2002) Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. J. Neurosci., 22 (24): 10662-70. [PMID:12486159]

15. Salinas M, Rash LD, Baron A, Lambeau G, Escoubas P, Lazdunski M. (2006) The receptor site of the spider toxin PcTx1 on the proton-gated cation channel ASIC1a. J Physiol, 570 (Pt 2): 339-54. [PMID:16284080]

16. Schmidt A, Rossetti G, Joussen S, Gründer S. (2017) Diminazene Is a Slow Pore Blocker of Acid-Sensing Ion Channel 1a (ASIC1a). Mol Pharmacol, 92 (6): 665-675. [PMID:29025967]

17. Smith ES, Cadiou H, McNaughton PA. (2007) Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action. Neuroscience, 145 (2): 686-98. [PMID:17258862]

18. Ugawa S, Ishida Y, Ueda T, Inoue K, Nagao M, Shimada S. (2007) Nafamostat mesilate reversibly blocks acid-sensing ion channel currents. Biochem Biophys Res Commun, 363 (1): 203-8. [PMID:17826743]

19. Voilley N, de Weille J, Mamet J, Lazdunski M. (2001) Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J. Neurosci., 21 (20): 8026-33. [PMID:11588175]

20. Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M. (1997) A proton-gated cation channel involved in acid-sensing. Nature, 386 (6621): 173-7. [PMID:9062189]

21. Wang W, Duan B, Xu H, Xu L, Xu TL. (2006) Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead. J Biol Chem, 281 (5): 2497-505. [PMID:16319075]

22. Yoder N, Yoshioka C, Gouaux E. (2018) Gating mechanisms of acid-sensing ion channels. Nature, 555 (7696): 397-401. [PMID:29513651]

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