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

被引：7
|
作者：
Pinheiro, Barbara Peixoto [1 ]
Mueller, Marcus [1 ]
Boes, Michael [2 ]
Guezguez, Jamil [3 ]
Burnet, Michael [3 ]
Tornincasa, Mara [4 ]
Rizzetto, Riccardo [4 ]
Rolland, Jean-Francois [4 ]
Liberati, Chiara [4 ]
Lohmer, Stefan [4 ]
Adel, Youssef [1 ]
Loewenheim, Hubert [1 ]
机构：
[1] Univ Tubingen, Dept Otolaryngol Head & Neck Surg, Tubingen Hearing Res Ctr, Translat Hearing Res, D-72076 Tubingen, Germany
[2] Acousia Therapeut, D-72070 Tubingen, Germany
[3] Synovo, D-72076 Tubingen, Germany
[4] Axxam, I-20091 Milan, Italy
来源：
CELL DEATH & DISEASE | 2022年 / 13卷 / 07期
关键词：
INNER-EAR; DEMENTIA PREVENTION; DOMINANT DEAFNESS; KCNQ4; COCHLEA; GENE; INTERVENTION; INHIBITION; MUTATIONS; BASES;
D O I：
10.1038/s41419-022-04915-5
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
引用
收藏
页数：9
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