Gap junctions and connexins in the inner ear: their roles in homeostasis and deafness.
OBJECTIVE
Mutations in GJB2 and GJB6, the genes encoding the gap-junction proteins connexin 26 and connexin 30, are the most common cause of autosomal recessive nonsyndromic deafness in many populations across the world. In this review, we discuss current ideas about the roles of gap junctions in the inner ear and the implications of connexin mutations on auditory function.


RESULTS
In recent years, a complex picture of the roles of gap junctions in cochlear physiology emerged. Rather than being mere conduits for the circulation of potassium ions in the inner ear, gap junctions have been implicated in intercellular signaling among nonsensory cells and may be involved in the maintenance of the endothelial barrier in the stria vascularis. Studies of mutant channels and mouse models for connexin-related deafness have provided valuable insights into some of the mechanisms by which connexin dysfunction causes cochlear degeneration. They have also identified potential therapeutic interventions for specific connexin mutations, such as the restoration of normal connexin 26 protein levels in GJB6-associated deafness.


CONCLUSIONS
Despite recent advances, a better understanding of the complexity of gap-junctional communication in the inner ear and the structure-function relationships of connexin proteins is required for the development of mechanism-based treatments of connexin-associated hearing loss.
Nickel
Regina
R
Centre for Auditory Research, UCL Ear Institute, University College London, London, UK. r.nickel@ucl.ac.uk
Forge
Andrew
A
D000818:Animals; D002450:Cell Communication / Q000235:genetics; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000503:physiopathology*; D005260:Female; D017629:Gap Junctions / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D034381:Hearing Loss / Q000235:genetics / Q000503:physiopathology; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D012680:Sensitivity and Specificity
D017630:Connexins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; D000072259:Connexin 26