ASIC1 | Acid-sensing (proton-gated) ion channels (ASICs) | IUPHAR/BPS Guide to PHARMACOLOGY

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ASIC1

target has curated data in GtoImmuPdb

Target id: 684

Nomenclature: ASIC1

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

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - - 12q12 ASIC1 acid sensing ion channel subunit 1
Mouse - - 15 F3 Asic1 acid-sensing (proton-gated) ion channel 1
Rat - - 7q36 Asic1 acid sensing ion channel subunit 1
Previous and Unofficial Names
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
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
UniProtKB
Wikipedia
Selected 3D Structures
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:  13
Functional Characteristics
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
H+

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Parameter Concentration range (M) Voltage-dependent (mV) Reference
Extracellular H+ 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 Affinity Parameter Concentration range (M) Voltage-dependent (mV) Reference
Pi-hexatoxin-Hi1a Hs - no ~9.3 pIC50 - no 4
pIC50 ~9.3 ASIC1a [4]
Not voltage dependent
psalmotoxin 1 Hs - no 9.0 pIC50 - no
pIC50 9.0 (IC50 9x10-10 M) ASIC1a
Not voltage dependent
Pi-theraphotoxin-Hm3a Hs - no ~8.5 pIC50 - no 8
pIC50 ~8.5 ASIC1a [8]
Not voltage dependent
Zn2+ Hs - no ~8.2 pIC50 - no
pIC50 ~8.2 (IC50 ~7x10-9 M) ASIC1a
Not voltage dependent
mambalgin-1 Hs - no ~7.0 – 7.3 pIC50 - no 2,6
pIC50 ~7.3 ASIC1a [6]
Not voltage dependent
pIC50 ~7.0 ASIC1b [2]
Not voltage dependent
diminazene Hs - no ~6.5 pIC50 - no 9
pIC50 ~6.5 ASIC1a & ASIC1b [9]
Not voltage dependent
A-317567 Rn - no ~5.7 pIC50 - no 7
pIC50 ~5.7 (IC50 ~2x10-6 M) ASIC1a [7]
Not voltage dependent
Pb2+ Hs - no ~5.4 – 5.8 pIC50 - no
pIC50 ~5.8 (IC50 ~1.5x10-6 M) ASIC1b
Not voltage dependent
pIC50 ~5.4 (IC50 ~4x10-6 M) ASIC1a
Not voltage dependent
benzamil Hs - no 5.0 pIC50 - no
pIC50 5.0 (IC50 1x10-5 M) ASIC1a
Not voltage dependent
ethylisopropylamiloride Hs - no 5.0 pIC50 - no
pIC50 5.0 (IC50 1x10-5 M) ASIC1a
Not voltage dependent
nafamostat Hs - no ~4.9 pIC50 - no
pIC50 ~4.9 (IC50 ~1.3x10-5 M) ASIC1a
Not voltage dependent
amiloride Hs - no 4.6 – 5.0 pIC50 - no
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
Not voltage dependent
ibuprofen Hs - no ~3.5 pIC50 - no
pIC50 ~3.5 (IC50 ~3.5x10-4 M) ASIC1a
Not voltage dependent
flurbiprofen Rn - no 3.5 pIC50 - no 12
pIC50 3.5 (IC50 3.5x10-4 M) ASIC1a [12]
Not voltage dependent
Ni2+ Hs - no ~3.2 pIC50 - no
pIC50 ~3.2 (IC50 ~6x10-4 M) ASIC1a
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 Affinity Parameter Reference
[125I]psalmotoxin 1 Hs - 9.7 pKd
pKd 9.7 (Kd 2.13x10-10 M) ASIC1a
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 [5,10-11]. The sustained current component mediated by ASIC3 is potentiated by hypertonic solutions in a manner that is synergistic with the effect of arachidonic acid [5].

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. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

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

Contributors

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How to cite this page

Stephan Kellenberger, Lachlan D. Rash, Laurent Schild.
Acid-sensing (proton-gated) ion channels (ASICs): ASIC1. Last modified on 28/03/2019. Accessed on 21/04/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=684.