Connexins and gap junctions in the inner ear--it's not just about K⁺ recycling.
Normal development, function and repair of the sensory epithelia in the inner ear are all dependent on gap junctional intercellular communication. Mutations in the connexin genes GJB2 and GJB6 (encoding CX26 and CX30) result in syndromic and non-syndromic deafness via various mechanisms. Clinical vestibular defects, however, are harder to connect with connexin dysfunction. Cx26 and Cx30 proteins are widely expressed in the epithelial and connective tissues of the cochlea, where they may form homomeric or heteromeric gap junction channels in a cell-specific and spatiotemporally complex fashion. Despite the study of mutant channels and animal models for both recessive and dominant autosomal deafness, it is still unclear why gap junctions are essential for auditory function, and why Cx26 and Cx30 do not compensate for each other in vivo. Cx26 appears to be essential for normal development of the auditory sensory epithelium, but may be dispensable during normal hearing. Cx30 appears to be essential for normal repair following sensory cell loss. The specific modes of intercellular signalling mediated by inner ear gap junction channels remain undetermined, but they are hypothesised to play essential roles in the maintenance of ionic and metabolic homeostasis in the inner ear. Recent studies have highlighted involvement of gap junctions in the transfer of essential second messengers between the non-sensory cells, and have proposed roles for hemichannels in normal hearing. Here, we summarise the current knowledge about the molecular and functional properties of inner ear gap junctions, and about tissue pathologies associated with connexin mutations.
UCL Ear Institute, University College London, 332 Gray's Inn Road, London, WC1X 8EE, UK, d.jagger@ucl.ac.uk.
Daniel J
DJ
Jagger
Andrew
A
Forge
D000818:Animals; D055592:Biophysical Phenomena; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D007758:Ear, Inner / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D011188:Potassium / Q000378:metabolism*
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D011188:Potassium