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Author Notes:

Correspondence: Xi Lin, E-mail: xlin2@emory.edu.

Conceived and designed the experiments: QC XL.

Performed the experiments: QC WT SA BZ XL.

Analyzed the data: QC WT BZ XL.

Contributed reagents/materials/analysis tools: XL.

Wrote the paper: QC SA XL.

We would like to thank Dr. Robert McKeon for carefully reading the manuscript and offering many helpful comments.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


Research Funding:

This study was supported by grants to X.Lin from National Institute on Deafness and other Communication Disorders (NIDCD, RO1-DC006483 and R21-DC008353) and Woodruff Foundation. W.Tang received grant supports from NIDCD (R21 DC008672) and the Deafness Research Foundation.

S.Ahmad is a recipient of NIDCD RO3 (R03-DC008693).

Gap Junction Mediated Intercellular Metabolite Transfer in the Cochlea Is Compromised in Connexin30 Null Mice


Journal Title:



Volume 3, Number 12


Type of Work:

Article | Final Publisher PDF


Connexin26 (Cx26) and connexin30 (Cx30) are two major protein subunits that co-assemble to form gap junctions (GJs) in the cochlea. Mutations in either one of them are the major cause of non-syndromic prelingual deafness in humans. Because the mechanisms of cochlear pathogenesis caused by Cx mutations are unclear, we investigated effects of Cx30 null mutation on GJ-mediated ionic and metabolic coupling in the cochlea of mice. A novel flattened cochlear preparation was used to directly assess intercellular coupling in the sensory epithelium of the cochlea. Double-electrode patch clamp recordings revealed that the absence of Cx30 did not significantly change GJ conductance among the cochlear supporting cells. The preserved electrical coupling is consistent with immunolabeling data showing extensive Cx26 GJs in the cochlea of the mutant mice. In contrast, dye diffusion assays showed that the rate and extent of intercellular transfer of multiple fluorescent dyes (including a non-metabolizable D-glucose analogue, 2-NBDG) among cochlear supporting cells were severely reduced in Cx30 null mice. Since the sensory epithelium in the cochlea is an avascular organ, GJ-facilitated intercellular transfer of nutrient and signaling molecules may play essential roles in cellular homeostasis. To test this possibility, NBDG was used as a tracer to study the contribution of GJs in transporting glucose into the cochlear sensory epithelium when delivered systemically. NBDG uptake in cochlear supporting cells was significantly reduced in Cx30 null mice. The decrease was also observed with GJ blockers or glucose competition, supporting the specificity of our tests. These data indicate that GJs facilitate efficient uptake of glucose in the supporting cells. This study provides the first direct experimental evidence showing that the transfer of metabolically-important molecules in cochlear supporting cells is dependent on the normal function of GJs, thereby suggesting a novel pathogenesis process in the cochlea for Cx-mutation-linked deafness.

Copyright information:

© 2008 Chang et al.

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