The Role of ASIC1a in Epilepsy: A Potential Therapeutic Target

Overview

Journal Curr Neuropharmacol

Publisher Bentham Science Publishers

Date 2021 Apr 2

PMID 33797385

Citations 5

Authors

Yu Cheng

Wuqiong Zhang

Yue Li

Ting Jiang

Buhajar Mamat

Yunhai Zhang

Famin Wang

Hongmei Meng

Affiliations

Soon will be listed here.

Abstract

Background: Epilepsy represents one of the most common brain diseases among humans. Tissue acidosis is a common phenomenon in epileptogenic foci. Moreover, its role in epileptogenesis remains unclear. Acid-sensing ion channel-1a (ASIC1a) represents a potential way to assess new therapies. ASIC1a, mainly expressed in the mammalian brain, is a type of protein-gated cation channel. It has been shown to play an important role in the pathological mechanism of various diseases, including stroke, epilepsy, and multiple sclerosis.

Methods: Data were collected from Web of Science, Medline, PubMed, through searching for these keywords: "Acid-sensing ion channels 1a" or "ASIC1a" and "epilepsy" or "seizure".

Results: The role of ASIC1a in epilepsy remains controversial; it may represent a promising therapeutic target of epilepsy.

Conclusion: This review is intended to provide an overview of the structure, trafficking, and molecular mechanisms of ASIC1a in order to elucidate the role of ASIC1a in epilepsy further.

Citing Articles

Astrocytic Acid-Sensing Ion Channel 1a Contributes to the Development of Epileptic Cognitive Impairment.

Li W, Zhou H, Li X, Hu G, Wei D Biomolecules. 2025; 15(1).

PMID: 39858536 PMC: 11764220. DOI: 10.3390/biom15010142.

Interaction Between Allopregnanolone and Amiloride Binding Sites on the GABA Receptor.

Bukanova J, Kondratenko R, Solntseva E Cell Biochem Biophys. 2024; .

PMID: 39730891 DOI: 10.1007/s12013-024-01654-6.

Mutagenesis of the Peptide Inhibitor of ASIC3 Channel Introduces Binding to Thumb Domain of ASIC1a but Reduces Analgesic Activity.

Khasanov T, Maleeva E, Koshelev S, Palikov V, Palikova Y, Dyachenko I Mar Drugs. 2024; 22(9).

PMID: 39330263 PMC: 11432795. DOI: 10.3390/md22090382.

A pH-sensitive closed-loop nanomachine to control hyperexcitability at the single neuron level.

Merolla A, Michetti C, Moschetta M, Vacca F, Ciano L, Emionite L Nat Commun. 2024; 15(1):5609.

PMID: 38965228 PMC: 11224301. DOI: 10.1038/s41467-024-49941-3.

4-(Azolyl)-Benzamidines as a Novel Chemotype for ASIC1a Inhibitors.

Platonov M, Maximyuk O, Rayevsky A, Hurmach V, Iegorova O, Naumchyk V Int J Mol Sci. 2024; 25(7).

PMID: 38612396 PMC: 11011685. DOI: 10.3390/ijms25073584.

References

Wang J, Liu F, Yang F, Wang Y, Qi X, Li Y . Disruption of auto-inhibition underlies conformational signaling of ASIC1a to induce neuronal necroptosis. Nat Commun. 2020; 11(1):475. PMC: 6981194. DOI: 10.1038/s41467-019-13873-0. View

Wu H, Wang C, Liu B, Li H, Zhang Y, Dong S . Altered Expression Pattern of Acid-Sensing Ion Channel Isoforms in Piriform Cortex After Seizures. Mol Neurobiol. 2015; 53(3):1782-1793. DOI: 10.1007/s12035-015-9130-5. View

Price M, Gong H, Parsons M, Kundert J, Reznikov L, Bernardinelli L . Localization and behaviors in null mice suggest that ASIC1 and ASIC2 modulate responses to aversive stimuli. Genes Brain Behav. 2013; 13(2):179-94. PMC: 3998777. DOI: 10.1111/gbb.12108. View

Velisek L, Dreier J, Stanton P, Heinemann U, Moshe S . Lowering of extracellular pH suppresses low-Mg(2+)-induces seizures in combined entorhinal cortex-hippocampal slices. Exp Brain Res. 1994; 101(1):44-52. DOI: 10.1007/BF00243215. View

Mango D, Braksator E, Battaglia G, Marcelli S, Mercuri N, Feligioni M . Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus. Pharmacol Res. 2017; 119:12-19. DOI: 10.1016/j.phrs.2017.01.028. View

Munro G, Christensen J, Erichsen H, Dyhring T, Demnitz J, Dam E . NS383 Selectively Inhibits Acid-Sensing Ion Channels Containing 1a and 3 Subunits to Reverse Inflammatory and Neuropathic Hyperalgesia in Rats. CNS Neurosci Ther. 2015; 22(2):135-45. PMC: 6492852. DOI: 10.1111/cns.12487. View

Nagaeva E, Tikhonova T, Magazanik L, Tikhonov D . Histamine selectively potentiates acid-sensing ion channel 1a. Neurosci Lett. 2016; 632:136-40. DOI: 10.1016/j.neulet.2016.08.047. View

Song X, Liu D, Qiang M, Li Q, Liu M, Li W . Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a. Neurosci Bull. 2020; 37(2):145-165. PMC: 7870742. DOI: 10.1007/s12264-020-00581-9. View

Alvarez de la Rosa D, Krueger S, Kolar A, Shao D, Fitzsimonds R, Canessa C . Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system. J Physiol. 2003; 546(Pt 1):77-87. PMC: 2342460. DOI: 10.1113/jphysiol.2002.030692. View

10.

Holland P, Akerman S, Andreou A, Karsan N, Wemmie J, Goadsby P . Acid-sensing ion channel 1: a novel therapeutic target for migraine with aura. Ann Neurol. 2012; 72(4):559-63. DOI: 10.1002/ana.23653. View

11.

Yermolaieva O, Leonard A, Schnizler M, Abboud F, Welsh M . Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a. Proc Natl Acad Sci U S A. 2004; 101(17):6752-7. PMC: 404117. DOI: 10.1073/pnas.0308636100. View

12.

Dussor G . ASICs as therapeutic targets for migraine. Neuropharmacology. 2015; 94:64-71. PMC: 4458434. DOI: 10.1016/j.neuropharm.2014.12.015. View

13.

Gruol D, Barker J, Huang L, MacDonald J, SMITH Jr T . Hydrogen ions have multiple effects on the excitability of cultured mammalian neurons. Brain Res. 1980; 183(1):247-52. DOI: 10.1016/0006-8993(80)90138-9. View

14.

Wang Q, Wang Q, Song X, Jiang Q, Wu Y, Li Y . Fear extinction requires ASIC1a-dependent regulation of hippocampal-prefrontal correlates. Sci Adv. 2018; 4(10):eaau3075. PMC: 6223961. DOI: 10.1126/sciadv.aau3075. View

15.

Liang J, Huang L, Chen X, Pan S, Lu Z, Xiao Z . Amiloride suppresses pilocarpine-induced seizures via ASICs other than NHE in rats. Int J Clin Exp Pathol. 2016; 8(11):14507-13. PMC: 4713556. View

16.

Somjen G . Acidification of interstitial fluid in hippocampal formation caused by seizures and by spreading depression. Brain Res. 1984; 311(1):186-8. DOI: 10.1016/0006-8993(84)91416-1. View

17.

Biagini G, Babinski K, Avoli M, Marcinkiewicz M, Seguela P . Regional and subunit-specific downregulation of acid-sensing ion channels in the pilocarpine model of epilepsy. Neurobiol Dis. 2001; 8(1):45-58. DOI: 10.1006/nbdi.2000.0331. View

18.

Herbert L, Resta T, Jernigan N . RhoA increases ASIC1a plasma membrane localization and calcium influx in pulmonary arterial smooth muscle cells following chronic hypoxia. Am J Physiol Cell Physiol. 2017; 314(2):C166-C176. PMC: 5866437. DOI: 10.1152/ajpcell.00159.2017. View

19.

Bolshakov K, Essin K, Buldakova S, Dorofeeva N, Skatchkov S, Eaton M . Characterization of acid-sensitive ion channels in freshly isolated rat brain neurons. Neuroscience. 2002; 110(4):723-30. DOI: 10.1016/s0306-4522(01)00582-6. View

20.

Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M . A proton-gated cation channel involved in acid-sensing. Nature. 1997; 386(6621):173-7. DOI: 10.1038/386173a0. View