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Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels
Two-pore domain potassium (K2P) channels are a diverse family of potassium channels. K2P channels generate background leak potassium currents to regulate cellular excitability and are thereby involved in a wide range of neurological disorders. K2P channels are modulated by a variety of physicochemic...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bentham Science Publishers
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199554/ https://www.ncbi.nlm.nih.gov/pubmed/33827408 http://dx.doi.org/10.2174/1570159X19666210407152528 |
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author | Huang, Lu Xu, Guangyin Jiang, Ruotian Luo, Yuncheng Zuo, Yunxia Liu, Jin |
author_facet | Huang, Lu Xu, Guangyin Jiang, Ruotian Luo, Yuncheng Zuo, Yunxia Liu, Jin |
author_sort | Huang, Lu |
collection | PubMed |
description | Two-pore domain potassium (K2P) channels are a diverse family of potassium channels. K2P channels generate background leak potassium currents to regulate cellular excitability and are thereby involved in a wide range of neurological disorders. K2P channels are modulated by a variety of physicochemical factors, such as mechanical stretch, temperature, and pH. In the peripheral nervous system, K2P channels are widely expressed in nociceptive neurons and play a critical role in pain perception. In this review, we summarize the recent advances in the pharmacological properties of K2P channels, with a focus on the exogenous small-molecule activators targeting K2P channels. We emphasize the subtype-selectivity, cellular and in vivo pharmacological properties of all the reported small-molecule activators. The key underlying analgesic mechanisms mediated by K2P are also summarized based on the data in the literature from studies using small-molecule activators and genetic knock-out animals. We discuss the advantages and limitations of the translational perspectives of K2P in pain medicine and provide outstanding questions for future studies in the end. |
format | Online Article Text |
id | pubmed-9199554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-91995542022-07-10 Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels Huang, Lu Xu, Guangyin Jiang, Ruotian Luo, Yuncheng Zuo, Yunxia Liu, Jin Curr Neuropharmacol Neurology Two-pore domain potassium (K2P) channels are a diverse family of potassium channels. K2P channels generate background leak potassium currents to regulate cellular excitability and are thereby involved in a wide range of neurological disorders. K2P channels are modulated by a variety of physicochemical factors, such as mechanical stretch, temperature, and pH. In the peripheral nervous system, K2P channels are widely expressed in nociceptive neurons and play a critical role in pain perception. In this review, we summarize the recent advances in the pharmacological properties of K2P channels, with a focus on the exogenous small-molecule activators targeting K2P channels. We emphasize the subtype-selectivity, cellular and in vivo pharmacological properties of all the reported small-molecule activators. The key underlying analgesic mechanisms mediated by K2P are also summarized based on the data in the literature from studies using small-molecule activators and genetic knock-out animals. We discuss the advantages and limitations of the translational perspectives of K2P in pain medicine and provide outstanding questions for future studies in the end. Bentham Science Publishers 2022-01-10 2022-01-10 /pmc/articles/PMC9199554/ /pubmed/33827408 http://dx.doi.org/10.2174/1570159X19666210407152528 Text en © 2022 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Neurology Huang, Lu Xu, Guangyin Jiang, Ruotian Luo, Yuncheng Zuo, Yunxia Liu, Jin Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels |
title | Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels |
title_full | Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels |
title_fullStr | Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels |
title_full_unstemmed | Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels |
title_short | Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels |
title_sort | development of non-opioid analgesics targeting two-pore domain potassium channels |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199554/ https://www.ncbi.nlm.nih.gov/pubmed/33827408 http://dx.doi.org/10.2174/1570159X19666210407152528 |
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