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


Journal

Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092

Informations de publication

Date de publication:
11 07 2022
Historique:
received: 07 02 2022
accepted: 04 05 2022
revised: 29 04 2022
entrez: 11 7 2022
pubmed: 12 7 2022
medline: 14 7 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35817766
doi: 10.1038/s41419-022-04915-5
pii: 10.1038/s41419-022-04915-5
pmc: PMC9273644
doi:

Substances chimiques

Potassium Channels 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

595

Informations de copyright

© 2022. The Author(s).

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Auteurs

Barbara Peixoto Pinheiro (B)

Translational Hearing Research, Tübingen Hearing Research Center, Department of Otolaryngology, Head & Neck Surgery, University of Tübingen, 72076, Tübingen, Germany. barbara.peixoto-pinheiro@uni-tuebingen.de.

Marcus Müller (M)

Translational Hearing Research, Tübingen Hearing Research Center, Department of Otolaryngology, Head & Neck Surgery, University of Tübingen, 72076, Tübingen, Germany.

Michael Bös (M)

Acousia Therapeutics, 72070, Tübingen, Germany.

Jamil Guezguez (J)

Synovo, 72076, Tübingen, Germany.

Michael Burnet (M)

Synovo, 72076, Tübingen, Germany.

Mara Tornincasa (M)

Axxam, Bresso, 20091, Milan, Italy.

Riccardo Rizzetto (R)

Axxam, Bresso, 20091, Milan, Italy.

Jean-Francois Rolland (JF)

Axxam, Bresso, 20091, Milan, Italy.

Chiara Liberati (C)

Axxam, Bresso, 20091, Milan, Italy.

Stefan Lohmer (S)

Axxam, Bresso, 20091, Milan, Italy.

Youssef Adel (Y)

Translational Hearing Research, Tübingen Hearing Research Center, Department of Otolaryngology, Head & Neck Surgery, University of Tübingen, 72076, Tübingen, Germany.

Hubert Löwenheim (H)

Translational Hearing Research, Tübingen Hearing Research Center, Department of Otolaryngology, Head & Neck Surgery, University of Tübingen, 72076, Tübingen, Germany. hubert.loewenheim@uni-tuebingen.de.

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Classifications MeSH