ASIC3 | Acid-sensing (proton-gated) ion channels (ASICs) | IUPHAR/BPS Guide to PHARMACOLOGY

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ASIC3

target has curated data in GtoImmuPdb

Target id: 686

Nomenclature: ASIC3

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 - - 7q35 ASIC3 acid sensing ion channel subunit 3
Mouse - - 5 A3 Asic3 acid-sensing (proton-gated) ion channel 3
Rat - - 4q11 Asic3 acid sensing ion channel subunit 3
Previous and Unofficial Names
DRASIC | TNaC1 | ACCN3 | amiloride-sensitive cation channel 3, testis | testis sodium channel 1 | acid sensing ion channel 3 | dorsal root ASIC | acid-sensing (proton-gated) ion channel 3 | acid sensing (proton gated) ion channel 3
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
UniProtKB
Wikipedia
Functional Characteristics
γ~ 13-15 pS;
biphasic response consisting of rapidly inactivating transient and sustained components;
very rapid activation (<5 ms) and inactivation (0.4 s);
fast recovery (0.4-0.6 s) @ pH 7.4, transient component partially inactivated at pH 7.2
Natural/Endogenous Ligands
H+

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

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
Extracellular H+ Hs - ~3.5 – 6.7 pEC50 - no
pEC50 ~6.2 – 6.7 (EC50 ~6.3x10-7 – 2x10-7 M) transient component
Not voltage dependent
pEC50 ~3.5 – 4.3 (EC50 ~3.5x10-4 – 5x10-5 M) sustained component
Not voltage dependent
GMQ Hs - ~3.0 pEC50 - no
pEC50 ~3.0 (EC50 ~1x10-3 M) largly non-desensitizing; at pH 7.4
Not voltage dependent
arcaine Hs - ~2.9 pEC50 - no
pEC50 ~2.9 (EC50 ~1.2x10-3 M) at pH 7.4
Not voltage dependent
agmatine Hs - ~2.0 pEC50 - no
pEC50 ~2.0 (EC50 ~9.8x10-3 M) at pH 7.4
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
APETx2 Hs - no 7.2 pIC50 - no
pIC50 7.2 (IC50 6.3x10-8 M) transient component only
Not voltage dependent
diminazene Hs - no ~6.5 pIC50 - no 4
pIC50 ~6.5 [4]
Not voltage dependent
A-317567 Hs - no 6.0 pIC50 - no 3
pIC50 6.0 (IC50 1.025x10-6 M) [3]
Not voltage dependent
Description: Human ASIC3 expressed in HEK293 cells
nafamostat Hs - no ~5.6 pIC50 - no
pIC50 ~5.6 (IC50 ~2.5x10-6 M) transient component
Not voltage dependent
amiloride Hs - no 4.2 – 4.8 pIC50 - no
pIC50 4.2 – 4.8 (IC50 6.3x10-5 – 1.6x10-5 M) transient component only - sustained component enhanced by 200μM amiloride at pH 4
Not voltage dependent
Gd3+ Hs - no 4.4 pIC50 - no
pIC50 4.4 (IC50 4x10-5 M)
Not voltage dependent
Zn2+ Hs - no 4.2 pIC50 - no
pIC50 4.2 (IC50 6.1x10-5 M)
Not voltage dependent
diclofenac Hs - no 4.0 pIC50 - no
pIC50 4.0 (IC50 9.2x10-5 M) sustained component
Not voltage dependent
aspirin Hs - no 4.0 pIC50 - no 7
pIC50 4.0 (IC50 9.2x10-5 M) sustained component [7]
Not voltage dependent
salicylic acid Hs - no 3.6 pIC50 - no
pIC50 3.6 (IC50 2.6x10-4 M) sustained component
Not voltage dependent
Immunopharmacology Comments
Non-steroidal anti-inflammatory drugs (NSAIDs) are direct inhibitors of ASIC currents (reviewed in [1]). Inflammatory conditions and particular pro-inflammatory mediators such as arachidonic acid induce overexpression of ASIC-encoding genes and enhance ASIC currents [2,5-6]. The sustained current component mediated by ASIC3 is potentiated by hypertonic solutions in a manner that is synergistic with the effect of arachidonic acid [2].

References

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

2. 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]

3. Kuduk SD, Di Marco CN, Bodmer-Narkevitch V, Cook SP, Cato MJ, Jovanovska A, Urban MO, Leitl M, Sain N, Liang A et al.. (2010) Synthesis, structure-activity relationship, and pharmacological profile of analogs of the ASIC-3 inhibitor A-317567. ACS Chem Neurosci, 1 (1): 19-24. [PMID:22778804]

4. 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]

5. 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]

6. 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]

7. 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]

Contributors

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How to cite this page

Stephan Kellenberger, Lachlan D. Rash, Laurent Schild.
Acid-sensing (proton-gated) ion channels (ASICs): ASIC3. Last modified on 07/03/2019. Accessed on 19/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=686.