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Gene Expression in the Human Endolymphatic Sac: The Solute Carrier Molecules in Endolymphatic Fluid Homeostasis

Møller, Martin Nue*; Kirkeby, Svend; Vikeså, Jonas; Nielsen, Finn Cilius; Cayé-Thomasen, Per

doi: 10.1097/MAO.0000000000000669
Basic Science

Objectives/Hypothesis: The purpose of the present study is to explore, demonstrate, and describe the expression of genes related to the solute carrier (SLC) molecules of ion transporters in the human endolymphatic sac.

Study Design: cDNA microarrays and immunohistochemistry were used for analyses of fresh human endolymphatic sac tissue samples.

Methods: Twelve tissue samples of the human endolymphatic sac were obtained during translabyrinthine surgery for vestibular schwannoma. Microarray technology was used to investigate tissue sample expression of solute carrier family genes, using adjacent dura mater as control. Immunohistochemistry was used for verification of translation of selected genes, as well as localization of the specific protein within the sac.

Results: An extensive representation of the SLC family genes were upregulated in the human endolymphatic sac, including SLC26a4 Pendrin, SLC4a1 sodium-bicarbonate transporter, SLC9a2 sodium-hydrogen transporter, SLC12a3 thiazide-sensitive Na-Cl transporter, and SLC34a2 sodium-phosphate transporter.

Conclusions: Several important ion transporters of the SLC family are expressed in the human endolymphatic sac, including Pendrin, the thiazide-sensitive Na-Cl transporter, and the Na-phosphate transporter SLC34a2. The data provide a new knowledge base considering the ion-dependent metabolic mechanisms maintaining inner ear homeostasis. More specifically, the results indicate a strong similarity with the ion transportation occurring in the kidney collecting ducts. In addition, the findings prompt a revision of the theories behind contemporary pharmacological treatment of Ménière’s disease and may broaden the understanding of the pathogenesis of BPPV.

*Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Rigshospitalet, Copenhagen; †Department of Oral Medicine, Dental School, Panum Institute, University of Copenhagen, Copenhagen; ‡Center for Genomic Medicine, University of Copenhagen, Rigshospitalet, Copenhagen; and §Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Address correspondence and reprint requests to Martin Nue Møller, M.D., Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Hospital Rigshospitalet/Gentofte, Copenhagen, 21009, Denmark; E-mail: martin@nuemoller.dk

Financial Disclosure: All financial support for this work was funded solely through public institutional funds.

The authors disclose no conflicts of interest.

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Copyright © 2015 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company