A molecular view of the function and pharmacology of acid-sensing ion channels.

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Serval ID
serval:BIB_F49EEB9636A6
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
A molecular view of the function and pharmacology of acid-sensing ion channels.
Journal
Pharmacological research
Author(s)
Vullo S., Kellenberger S.
ISSN
1096-1186 (Electronic)
ISSN-L
1043-6618
Publication state
Published
Issued date
04/2020
Peer-reviewed
Oui
Volume
154
Pages
104166
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Abstract
The pH in the different tissues and organs of our body is kept within tight limits. Local pH changes occur, however, temporarily under physiological conditions, as for example in synapses during neuronal activity. In pathological situations, such as in ischemia, inflammation, and tumor growth, long-lasting acidification develops. Acid-sensing ion channels (ASICs) are low pH-activated Na <sup>+</sup> -permeable ion channels that are widely expressed in the central and peripheral nervous systems. ASICs act as pH sensors, leading to neuronal excitation when the pH drops. Animal studies have shown that ASICs are involved in several physiological and pathological processes, such as pain sensation, learning, fear sensing, and neurodegeneration after ischemic stroke. ASIC inhibitors could be used as analgesic and anxiolytic drugs, and as drugs for the treatment of ischemic stroke. For these reasons, ASICs have recently attracted increasing attention. Currently, no drugs are clinically used as ASIC modulators. ASICs are however targets of several peptide toxins from animals. Much effort is invested in research studying the function of these channels. We review here the available pharmacological agents acting on ASICs, which include small molecules and animal toxins. We then discuss the current understanding of the molecular mechanisms by which pH controls ASIC activity. Knowledge of the function of ASICs at the molecular level should allow the development of new pharmacological strategies for targeting these promising ion channels.
Keywords
2-(4-Methylquinazolin-2-yl)guanidine (PubChem CID: 345657), APETx2 (PubChem CID: 90488973), ASIC, Amiloride (PubChem CID: 16231), Arachidonic acid (PubChem CID: 444899), Diminazene (PubChem CID: 2354), Mambalgin (PubChem CID: 121513904), Psalmotoxin1 (PubChem CID: 90489000), activation mechanism, desensitization, ion channel, neuron, pharmacology, Activation mechanism, Desensitization, Ion channel, Neuron, Pharmacology
Pubmed
Open Access
Yes
Create date
12/02/2019 8:48
Last modification date
17/09/2020 8:13
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