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Acid-sensing ion channel 3: An analgesic target
Acid-sensing ion channel 3 (ASIC3) belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. There are 7 different ASIC subunits encoded by 5 different genes. Most ASIC subunits form trimeric ion channels that upon activation by extracellular protons mediate a transient inward curre...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801124/ https://www.ncbi.nlm.nih.gov/pubmed/33258401 http://dx.doi.org/10.1080/19336950.2020.1852831 |
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author | Dulai, Jasdip Singh Smith, Ewan St. John Rahman, Taufiq |
author_facet | Dulai, Jasdip Singh Smith, Ewan St. John Rahman, Taufiq |
author_sort | Dulai, Jasdip Singh |
collection | PubMed |
description | Acid-sensing ion channel 3 (ASIC3) belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. There are 7 different ASIC subunits encoded by 5 different genes. Most ASIC subunits form trimeric ion channels that upon activation by extracellular protons mediate a transient inward current inducing cellular excitability. ASIC subunits exhibit differential tissue expression and biophysical properties, and the ability of subunits to form homo- and heteromeric trimers further increases the complexity of currents measured and their pharmacological properties. ASIC3 is of particular interest, not only because it exhibits high expression in sensory neurones, but also because upon activation it does not fully inactivate: a transient current is followed by a sustained current that persists during a period of extracellular acidity, i.e. ASIC3 can encode prolonged acidosis as a nociceptive signal. Furthermore, certain mediators sensitize ASIC3 enabling smaller proton concentrations to activate it and other mediators can directly activate the channel at neutral pH. Moreover, there is a plethora of evidence using transgenic mouse models and pharmacology, which supports ASIC3 as being a potential target for development of analgesics. This review will focus on current understanding of ASIC3 function to provide an overview of how ASIC3 contributes to physiology and pathophysiology, examining the mechanisms by which it can be modulated, and highlighting gaps in current understanding and future research directions. |
format | Online Article Text |
id | pubmed-7801124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-78011242021-01-21 Acid-sensing ion channel 3: An analgesic target Dulai, Jasdip Singh Smith, Ewan St. John Rahman, Taufiq Channels (Austin) Review Acid-sensing ion channel 3 (ASIC3) belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. There are 7 different ASIC subunits encoded by 5 different genes. Most ASIC subunits form trimeric ion channels that upon activation by extracellular protons mediate a transient inward current inducing cellular excitability. ASIC subunits exhibit differential tissue expression and biophysical properties, and the ability of subunits to form homo- and heteromeric trimers further increases the complexity of currents measured and their pharmacological properties. ASIC3 is of particular interest, not only because it exhibits high expression in sensory neurones, but also because upon activation it does not fully inactivate: a transient current is followed by a sustained current that persists during a period of extracellular acidity, i.e. ASIC3 can encode prolonged acidosis as a nociceptive signal. Furthermore, certain mediators sensitize ASIC3 enabling smaller proton concentrations to activate it and other mediators can directly activate the channel at neutral pH. Moreover, there is a plethora of evidence using transgenic mouse models and pharmacology, which supports ASIC3 as being a potential target for development of analgesics. This review will focus on current understanding of ASIC3 function to provide an overview of how ASIC3 contributes to physiology and pathophysiology, examining the mechanisms by which it can be modulated, and highlighting gaps in current understanding and future research directions. Taylor & Francis 2021-01-04 /pmc/articles/PMC7801124/ /pubmed/33258401 http://dx.doi.org/10.1080/19336950.2020.1852831 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Dulai, Jasdip Singh Smith, Ewan St. John Rahman, Taufiq Acid-sensing ion channel 3: An analgesic target |
title | Acid-sensing ion channel 3: An analgesic target |
title_full | Acid-sensing ion channel 3: An analgesic target |
title_fullStr | Acid-sensing ion channel 3: An analgesic target |
title_full_unstemmed | Acid-sensing ion channel 3: An analgesic target |
title_short | Acid-sensing ion channel 3: An analgesic target |
title_sort | acid-sensing ion channel 3: an analgesic target |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801124/ https://www.ncbi.nlm.nih.gov/pubmed/33258401 http://dx.doi.org/10.1080/19336950.2020.1852831 |
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