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Review
. 2022 Sep 15:15:976388.
doi: 10.3389/fnmol.2022.976388. eCollection 2022.

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

Penghui Chen  1   2   3 , Wenjin Wu  1   2   3 , Jifang Zhang  1   2   3 , Junmin Chen  1   2   3 , Yue Li  1   2   3 , Lianhua Sun  1   2   3 , Shule Hou  1   2   3 , Jun Yang  1   2   3
Affiliations
Review

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

Penghui Chen et al. Front Mol Neurosci. .

Abstract

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.

Keywords: cochlea; connexin; gap junction; hearing loss; mechanism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic diagrams of Cx expression, potassium recycling, and ATP-Ca2+ signaling in the inner ear.
FIGURE 2
FIGURE 2
Schematic diagrams of glucose transport in the stria vascularis and spiral ligament of the cochlea.
See this image and copyright information in PMC

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