A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss

Age-related hearing loss (ARHL) is the most common sensory impairment mainly caused by degeneration of sensory hair cells in the cochlea with no causal medical treatment available. Auditory function and sensory hair cell survival critically depend on the Kv7.4 (KCNQ4) channel, a voltage-gated potass...

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Autores principales: Peixoto Pinheiro, Barbara, Müller, Marcus, Bös, Michael, Guezguez, Jamil, Burnet, Michael, Tornincasa, Mara, Rizzetto, Riccardo, Rolland, Jean-Francois, Liberati, Chiara, Lohmer, Stefan, Adel, Youssef, Löwenheim, Hubert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273644/
https://www.ncbi.nlm.nih.gov/pubmed/35817766
http://dx.doi.org/10.1038/s41419-022-04915-5
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author Peixoto Pinheiro, Barbara
Müller, Marcus
Bös, Michael
Guezguez, Jamil
Burnet, Michael
Tornincasa, Mara
Rizzetto, Riccardo
Rolland, Jean-Francois
Liberati, Chiara
Lohmer, Stefan
Adel, Youssef
Löwenheim, Hubert
author_facet Peixoto Pinheiro, Barbara
Müller, Marcus
Bös, Michael
Guezguez, Jamil
Burnet, Michael
Tornincasa, Mara
Rizzetto, Riccardo
Rolland, Jean-Francois
Liberati, Chiara
Lohmer, Stefan
Adel, Youssef
Löwenheim, Hubert
author_sort Peixoto Pinheiro, Barbara
collection PubMed
description Age-related hearing loss (ARHL) is the most common sensory impairment mainly caused by degeneration of sensory hair cells in the cochlea with no causal medical treatment available. Auditory function and sensory hair cell survival critically depend on the Kv7.4 (KCNQ4) channel, a voltage-gated potassium channel expressed in outer hair cells (OHCs), with its impaired function or reduced activity previously associated with ARHL. Here, we investigated the effect of a potent small-molecule Kv7.4 agonist on ARHL in the senescence-accelerated mouse prone 8 (SAMP8) model. For the first time in vivo, we show that Kv7.4 activation can significantly reduce age-related threshold shifts of auditory brainstem responses as well as OHC loss in the SAMP8 model. Pharmacological activation of Kv7.4 thus holds great potential as a therapeutic approach for ARHL as well as other hearing impairments related to Kv7.4 function.
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spelling pubmed-92736442022-07-13 A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss Peixoto Pinheiro, Barbara Müller, Marcus Bös, Michael Guezguez, Jamil Burnet, Michael Tornincasa, Mara Rizzetto, Riccardo Rolland, Jean-Francois Liberati, Chiara Lohmer, Stefan Adel, Youssef Löwenheim, Hubert Cell Death Dis Article Age-related hearing loss (ARHL) is the most common sensory impairment mainly caused by degeneration of sensory hair cells in the cochlea with no causal medical treatment available. Auditory function and sensory hair cell survival critically depend on the Kv7.4 (KCNQ4) channel, a voltage-gated potassium channel expressed in outer hair cells (OHCs), with its impaired function or reduced activity previously associated with ARHL. Here, we investigated the effect of a potent small-molecule Kv7.4 agonist on ARHL in the senescence-accelerated mouse prone 8 (SAMP8) model. For the first time in vivo, we show that Kv7.4 activation can significantly reduce age-related threshold shifts of auditory brainstem responses as well as OHC loss in the SAMP8 model. Pharmacological activation of Kv7.4 thus holds great potential as a therapeutic approach for ARHL as well as other hearing impairments related to Kv7.4 function. Nature Publishing Group UK 2022-07-11 /pmc/articles/PMC9273644/ /pubmed/35817766 http://dx.doi.org/10.1038/s41419-022-04915-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Peixoto Pinheiro, Barbara
Müller, Marcus
Bös, Michael
Guezguez, Jamil
Burnet, Michael
Tornincasa, Mara
Rizzetto, Riccardo
Rolland, Jean-Francois
Liberati, Chiara
Lohmer, Stefan
Adel, Youssef
Löwenheim, Hubert
A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss
title A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss
title_full A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss
title_fullStr A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss
title_full_unstemmed A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss
title_short A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss
title_sort potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273644/
https://www.ncbi.nlm.nih.gov/pubmed/35817766
http://dx.doi.org/10.1038/s41419-022-04915-5
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