Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear

Hong Bo Zhao, Ning Yu, Carrie R. Fleming

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

Connexin gap junctions play an important role in hearing function, but the mechanism by which this contribution occurs is unknown. Connexins in the cochlea are expressed only in supporting cells; no connexin expression occurs in auditory sensory hair cells. A gap junctional channel is formed by two hemichannels. Here, we show that connexin hemichannels in the cochlea can release ATP at levels that account for the submicromolar concentrations measured in the cochlear fluids in vivo. The release could be increased 3- to 5-fold by a reduction of extracellular Ca2+ or an increase in membrane stress, and blocked by gap junctional blockers. We also demonstrated that extracellular ATP at submicromolar levels apparently affected outer hair cell (OHC) electromotility, which is an active cochlear amplifier determining cochlear sensitivity to sound stimulation in mammals. ATP reduced OHC electromotility and the slope factor of the voltage dependence and shifted the operating point to reduce the active amplifier gain. ATP also reduced the generation of distortion products. Immunofluorescent staining showed that purinergic receptors P2×2 and P2×7 were distributed on the OHC surface. Blockage of P2 receptors eliminated the effect of ATP on the OHC electromotility. The data revealed that there is a hemichannel-mediated, purinergic intercellular signaling pathway between supporting cells and hair cells in the cochlea to control hearing sensitivity. The data also demonstrated a potential source of ATP in the cochlea.

Original languageEnglish
Pages (from-to)18724-18729
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number51
DOIs
StatePublished - Dec 20 2005

Keywords

  • Active cochlear mechanics
  • Cochlear supporting cells
  • Connexin
  • Outer hair cell electromotility
  • P2 receptor

ASJC Scopus subject areas

  • General

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