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Homeostasis in the inner ear

Summary

Normal hearing relies on the maintenance of a constant chemical environment within the tissues of the inner ear. This so-called “homeostasis” protects the sensory “hair cells” from damage, ensuring the exquisite sensitivity and frequency selectivity of our hearing. Inner ear homeostasis is carried out by numerous cellular mechanisms, often which are reliant on each other. Failure of any of these processes can result in hair cell death, and permanent hearing loss. It is our aim to gain a better understanding of these mechanisms, and to learn how we can translate these findings into clinical treatments to prevent hearing loss

Continuing recent research, we are working closely with Andy Forge’s lab to decipher the regulation of homeostasis in the cochlea and vestibular organs, including changes occurring during ageing and regeneration. In particular, we are studying the function of connexins (gap junction channel subunits) in supporting cells, and how they work to protect hair cells from damage. During his PhD funded by Deafness Research UK, John Kelly has mapped the development of gap junctional intercellular communication (GJIC) within the cochlear lateral wall, demonstrating a cytoplasmic continuity between spiral ligament fibrocytes and basal cells and intermediate cells in stria vascularis. In other work we collaborate with David Kelsell (Barts & The London, Queen Mary University) to study human connexin mutations, and David Furness (University of Keele) to examine the role of glutamate transporters in the lateral wall.

 Relevant Publications

  • Kelly JJ, Forge A, Jagger DJ. Development of gap junctional intercellular communication within the lateral wall of the rat cochlea. Neuroscience 180, 360-369, 2011.
  • Jagger DJ, Nevill G, Forge A. The Membrane Properties of Cochlear Root Cells are Consistent with Roles in Potassium Recirculation and Spatial Buffering. JARO 11, 435-448, 2010.
  • Furness DN, Lawton DM, Mahendrasingam S, Hodierne L, Jagger DJ. Quantitative analysis of the expression of the glutamate-aspartate transporter and identification of functional glutamate uptake reveal a role for cochlear fibrocytes in glutamate homeostasis. Neuroscience 162, 1307-1321, 2009.
  • Matos TD, Caria H, Simões-Teixeira H, Aasen T, Nickel R, Jagger DJ, O'Neill A, Kelsell DP, Fialho G. A novel hearing-loss-related mutation occurring in the GJB2 basal promoter. Journal of Medical Genetics 44, 721-725, 2007.
  • Jagger DJ, Forge A. Compartmentalized and signal-selective gap junctional coupling in the hearing cochlea. Journal of Neuroscience 26, 1260-1268, 2006.

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