Selective Modulation of K(+) Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons

The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role fo...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Chen, Su, Min, Wang, Yingzi, Li, Xinmeng, Zhang, Yongxue, Du, Xiaona, Zhang, Hailin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Neuroscience
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735115/
https://www.ncbi.nlm.nih.gov/pubmed/29311835
http://dx.doi.org/10.3389/fncel.2017.00405
_version_ 1783287137593982976
author Zhao, Chen
Su, Min
Wang, Yingzi
Li, Xinmeng
Zhang, Yongxue
Du, Xiaona
Zhang, Hailin
author_facet Zhao, Chen
Su, Min
Wang, Yingzi
Li, Xinmeng
Zhang, Yongxue
Du, Xiaona
Zhang, Hailin
author_sort Zhao, Chen
collection PubMed
description The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K(+) channel modulators.
format Online
Article
Text
id pubmed-5735115
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-57351152018-01-08 Selective Modulation of K(+) Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons Zhao, Chen Su, Min Wang, Yingzi Li, Xinmeng Zhang, Yongxue Du, Xiaona Zhang, Hailin Front Cell Neurosci Neuroscience The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K(+) channel modulators. Frontiers Media S.A. 2017-12-14 /pmc/articles/PMC5735115/ /pubmed/29311835 http://dx.doi.org/10.3389/fncel.2017.00405 Text en Copyright © 2017 Zhao, Su, Wang, Li, Zhang, Du and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Zhao, Chen
Su, Min
Wang, Yingzi
Li, Xinmeng
Zhang, Yongxue
Du, Xiaona
Zhang, Hailin
Selective Modulation of K(+) Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons
title Selective Modulation of K(+) Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons
title_full Selective Modulation of K(+) Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons
title_fullStr Selective Modulation of K(+) Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons
title_full_unstemmed Selective Modulation of K(+) Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons
title_short Selective Modulation of K(+) Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons
title_sort selective modulation of k(+) channel kv7.4 significantly affects the excitability of drn 5-ht neurons
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735115/
https://www.ncbi.nlm.nih.gov/pubmed/29311835
http://dx.doi.org/10.3389/fncel.2017.00405
work_keys_str_mv AT zhaochen selectivemodulationofkchannelkv74significantlyaffectstheexcitabilityofdrn5htneurons
AT sumin selectivemodulationofkchannelkv74significantlyaffectstheexcitabilityofdrn5htneurons
AT wangyingzi selectivemodulationofkchannelkv74significantlyaffectstheexcitabilityofdrn5htneurons
AT lixinmeng selectivemodulationofkchannelkv74significantlyaffectstheexcitabilityofdrn5htneurons
AT zhangyongxue selectivemodulationofkchannelkv74significantlyaffectstheexcitabilityofdrn5htneurons
AT duxiaona selectivemodulationofkchannelkv74significantlyaffectstheexcitabilityofdrn5htneurons
AT zhanghailin selectivemodulationofkchannelkv74significantlyaffectstheexcitabilityofdrn5htneurons

Ejemplares similares