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Spider venom-derived peptide induces hyperalgesia in Na(v)1.7 knockout mice by activating Na(v)1.9 channels
The sodium channels Na(v)1.7, Na(v)1.8 and Na(v)1.9 are critical for pain perception in peripheral nociceptors. Loss of function of Na(v)1.7 leads to congenital insensitivity to pain in humans. Here we show that the spider peptide toxin called HpTx1, first identified as an inhibitor of K(v)4.2, rest...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210961/ https://www.ncbi.nlm.nih.gov/pubmed/32385249 http://dx.doi.org/10.1038/s41467-020-16210-y |
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author | Zhou, Xi Ma, Tingbin Yang, Luyao Peng, Shuijiao Li, Lulu Wang, Zhouquan Xiao, Zhen Zhang, Qingfeng Wang, Li Huang, Yazhou Chen, Minzhi Liang, Songping Zhang, Xianwei Liu, Jing Yu Liu, Zhonghua |
author_facet | Zhou, Xi Ma, Tingbin Yang, Luyao Peng, Shuijiao Li, Lulu Wang, Zhouquan Xiao, Zhen Zhang, Qingfeng Wang, Li Huang, Yazhou Chen, Minzhi Liang, Songping Zhang, Xianwei Liu, Jing Yu Liu, Zhonghua |
author_sort | Zhou, Xi |
collection | PubMed |
description | The sodium channels Na(v)1.7, Na(v)1.8 and Na(v)1.9 are critical for pain perception in peripheral nociceptors. Loss of function of Na(v)1.7 leads to congenital insensitivity to pain in humans. Here we show that the spider peptide toxin called HpTx1, first identified as an inhibitor of K(v)4.2, restores nociception in Na(v)1.7 knockout (Na(v)1.7-KO) mice by enhancing the excitability of dorsal root ganglion neurons. HpTx1 inhibits Na(v)1.7 and activates Na(v)1.9 but does not affect Na(v)1.8. This toxin produces pain in wild-type (WT) and Na(v)1.7-KO mice, and attenuates nociception in Na(v)1.9-KO mice, but has no effect in Na(v)1.8-KO mice. These data indicate that HpTx1-induced hypersensitivity is mediated by Na(v)1.9 activation and offers pharmacological insight into the relationship of the three Na(v) channels in pain signalling. |
format | Online Article Text |
id | pubmed-7210961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72109612020-05-13 Spider venom-derived peptide induces hyperalgesia in Na(v)1.7 knockout mice by activating Na(v)1.9 channels Zhou, Xi Ma, Tingbin Yang, Luyao Peng, Shuijiao Li, Lulu Wang, Zhouquan Xiao, Zhen Zhang, Qingfeng Wang, Li Huang, Yazhou Chen, Minzhi Liang, Songping Zhang, Xianwei Liu, Jing Yu Liu, Zhonghua Nat Commun Article The sodium channels Na(v)1.7, Na(v)1.8 and Na(v)1.9 are critical for pain perception in peripheral nociceptors. Loss of function of Na(v)1.7 leads to congenital insensitivity to pain in humans. Here we show that the spider peptide toxin called HpTx1, first identified as an inhibitor of K(v)4.2, restores nociception in Na(v)1.7 knockout (Na(v)1.7-KO) mice by enhancing the excitability of dorsal root ganglion neurons. HpTx1 inhibits Na(v)1.7 and activates Na(v)1.9 but does not affect Na(v)1.8. This toxin produces pain in wild-type (WT) and Na(v)1.7-KO mice, and attenuates nociception in Na(v)1.9-KO mice, but has no effect in Na(v)1.8-KO mice. These data indicate that HpTx1-induced hypersensitivity is mediated by Na(v)1.9 activation and offers pharmacological insight into the relationship of the three Na(v) channels in pain signalling. Nature Publishing Group UK 2020-05-08 /pmc/articles/PMC7210961/ /pubmed/32385249 http://dx.doi.org/10.1038/s41467-020-16210-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhou, Xi Ma, Tingbin Yang, Luyao Peng, Shuijiao Li, Lulu Wang, Zhouquan Xiao, Zhen Zhang, Qingfeng Wang, Li Huang, Yazhou Chen, Minzhi Liang, Songping Zhang, Xianwei Liu, Jing Yu Liu, Zhonghua Spider venom-derived peptide induces hyperalgesia in Na(v)1.7 knockout mice by activating Na(v)1.9 channels |
title | Spider venom-derived peptide induces hyperalgesia in Na(v)1.7 knockout mice by activating Na(v)1.9 channels |
title_full | Spider venom-derived peptide induces hyperalgesia in Na(v)1.7 knockout mice by activating Na(v)1.9 channels |
title_fullStr | Spider venom-derived peptide induces hyperalgesia in Na(v)1.7 knockout mice by activating Na(v)1.9 channels |
title_full_unstemmed | Spider venom-derived peptide induces hyperalgesia in Na(v)1.7 knockout mice by activating Na(v)1.9 channels |
title_short | Spider venom-derived peptide induces hyperalgesia in Na(v)1.7 knockout mice by activating Na(v)1.9 channels |
title_sort | spider venom-derived peptide induces hyperalgesia in na(v)1.7 knockout mice by activating na(v)1.9 channels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210961/ https://www.ncbi.nlm.nih.gov/pubmed/32385249 http://dx.doi.org/10.1038/s41467-020-16210-y |
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