Gap Junctions and Connexins in the Inner Ear: Their Roles in Homeostasis and Deafness

Curr Opin Otolaryngol Head Neck Surg. 2008 Oct;16(5):452-7. doi: 10.1097/MOO.0b013e32830e20b0.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Communication / genetics
  • Connexin 26
  • Connexins / genetics*
  • Connexins / metabolism
  • DNA Mutational Analysis
  • Deafness / genetics*
  • Deafness / physiopathology
  • Disease Models, Animal
  • Ear, Inner / physiopathology*
  • Female
  • Gap Junctions / genetics*
  • Gap Junctions / physiology
  • Gene Expression Regulation
  • Genetic Predisposition to Disease*
  • Hearing Loss / genetics
  • Hearing Loss / physiopathology
  • Homeostasis / genetics
  • Humans
  • Male
  • Mice
  • Mutation*
  • Sensitivity and Specificity

Substances

  • Connexins
  • DFNA3 protein, human
  • Gjb2 protein, mouse
  • Connexin 26