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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Bibliographic Details
Published in:Cell death & disease 2022-07, Vol.13 (7), p.595-595, Article 595
Main Authors: 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
Format: Article
Language:English
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Age
Agonists
Animals
Antibodies
Auditory system
Biochemistry
Biomedical and Life Sciences
Brain stem
Cell Biology
Cell Culture
Cell survival
Cochlea
Degeneration
Disease Models, Animal
Ears & hearing
Hair
Hair cells
Hair Cells, Auditory, Outer
Hearing
Hearing loss
Hearing Loss - drug therapy
Immunology
KCNQ4 protein
Life Sciences
Medical treatment
Mice
Mutation
Outer hair cells
Potassium
Potassium Channels
Potassium channels (voltage-gated)
Senescence
Signal transduction
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Summary: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.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-022-04915-5