Pathological mechanisms of connexin26-related hearing loss: Potassium recycling, ATP-calcium signaling, or energy supply?

Penghui Chen; Penghui Chen; Penghui Chen; Wenjin Wu; Wenjin Wu; Wenjin Wu; Jifang Zhang; Jifang Zhang; Jifang Zhang; Junmin Chen; Junmin Chen; Junmin Chen; Yue Li; Yue Li; Yue Li; Lianhua Sun; Lianhua Sun; Lianhua Sun; Shule Hou; Shule Hou; Shule Hou; Jun Yang; Jun Yang; Jun Yang

doi:10.3389/fnmol.2022.976388

Frontiers in Molecular Neuroscience (Sep 2022)

Pathological mechanisms of connexin26-related hearing loss: Potassium recycling, ATP-calcium signaling, or energy supply?

Penghui Chen,
Penghui Chen,
Penghui Chen,
Wenjin Wu,
Wenjin Wu,
Wenjin Wu,
Jifang Zhang,
Jifang Zhang,
Jifang Zhang,
Junmin Chen,
Junmin Chen,
Junmin Chen,
Yue Li,
Yue Li,
Yue Li,
Lianhua Sun,
Lianhua Sun,
Lianhua Sun,
Shule Hou,
Shule Hou,
Shule Hou,
Jun Yang,
Jun Yang,
Jun Yang

Affiliations

Penghui Chen: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Penghui Chen: Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
Penghui Chen: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Wenjin Wu: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Wenjin Wu: Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
Wenjin Wu: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Jifang Zhang: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Jifang Zhang: Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
Jifang Zhang: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Junmin Chen: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Junmin Chen: Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
Junmin Chen: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Yue Li: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yue Li: Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
Yue Li: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Lianhua Sun: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Lianhua Sun: Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
Lianhua Sun: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Shule Hou: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shule Hou: Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
Shule Hou: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Jun Yang: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Jun Yang: Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
Jun Yang: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China

DOI: https://doi.org/10.3389/fnmol.2022.976388
Journal volume & issue: Vol. 15

Abstract

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Hereditary deafness is one of the most common human birth defects. GJB2 gene mutation is the most genetic etiology. Gap junction protein 26 (connexin26, Cx26) encoded by the GJB2 gene, which is responsible for intercellular substance transfer and signal communication, plays a critical role in hearing acquisition and maintenance. The auditory character of different Connexin26 transgenic mice models can be classified into two types: profound congenital deafness and late-onset progressive hearing loss. Recent studies demonstrated that there are pathological changes including endocochlear potential reduction, active cochlear amplification impairment, cochlear developmental disorders, and so on, in connexin26 deficiency mice. Here, this review summarizes three main hypotheses to explain pathological mechanisms of connexin26-related hearing loss: potassium recycling disruption, adenosine-triphosphate-calcium signaling propagation disruption, and energy supply dysfunction. Elucidating pathological mechanisms underlying connexin26-related hearing loss can help develop new protective and therapeutic strategies for this common deafness. It is worthy of further study on the detailed cellular and molecular upstream mechanisms to modify connexin (channel) function.

Published in Frontiers in Molecular Neuroscience

ISSN: 1662-5099 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.frontiersin.org/journals/molecular-neuroscience

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