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"Reversed polarization" of Na/K-ATPase — a sign of inverted transport in the human endolymphatic sac: a super-resolution structured illumination microscopy (SR-SIM) study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.ORCID iD: 0000-0001-5825-9160
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.ORCID iD: 0000-0002-0687-3457
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
2020 (English)In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 379, no 3, p. 445-457Article in journal (Refereed) Published
Abstract [en]

The human endolymphatic sac (ES) is believed to regulate inner ear fluid homeostasis and to be associated with Meniere's disease (MD). We analyzed the ion transport protein sodium/potassium-ATPase (Na/K-ATPase) and its isoforms in the human ES using super-resolution structured illumination microscopy (SR-SIM). Human vestibular aqueducts were collected during trans-labyrinthine vestibular schwannoma surgery after obtaining ethical permission. Antibodies against various isoforms of Na/K-ATPase and additional solute-transporting proteins, believed to be essential for ion and fluid transport, were used for immunohistochemistry. A population of epithelial cells of the human ES strongly expressed Na/K-ATPase α1, β1, and β3 subunit isoforms in either the lateral/basolateral or apical plasma membrane domains. The β1 isoform was expressed in the lateral/basolateral plasma membranes in mostly large cylindrical cells, while β3 and α1 both were expressed with "reversed polarity" in the apical cell membrane in lower epithelial cells. The heterogeneous expression of Na/K-ATPase subunits substantiates earlier notions that the ES is a dynamic structure where epithelial cells show inverted epithelial transport. Dual absorption and secretion processes may regulate and maintain inner ear fluid homeostasis. These findings may shed new light on the etiology of endolymphatic hydrops and MD.

Place, publisher, year, edition, pages
Springer Nature , 2020. Vol. 379, no 3, p. 445-457
Keywords [en]
Endolymphatic sac, Human, Na/K-ATPase, Reversed polarity, SIM
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-406751DOI: 10.1007/s00441-019-03106-7ISI: 000495969500003PubMedID: 31713726OAI: oai:DiVA.org:uu-406751DiVA, id: diva2:1413989
Available from: 2020-03-11 Created: 2020-03-11 Last updated: 2021-03-25Bibliographically approved
In thesis
1. The Human Vestibular Aqueduct, Endolymphatic Duct and Sac: A Morphological Study Using Micro-CT, Super Resolution Immunohistochemistry and Synchrotron Phase Contrast Imaging
Open this publication in new window or tab >>The Human Vestibular Aqueduct, Endolymphatic Duct and Sac: A Morphological Study Using Micro-CT, Super Resolution Immunohistochemistry and Synchrotron Phase Contrast Imaging
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The inner ear lies sheltered in the temporal bone and consists of basically three parts: the cochlea (the hearing organ), the vestibular (the balance organ), and the endolymphatic duct (ED) and endolymphatic sac (ES). The ES and ED are located in a bony canal, the vestibular aqueduct (VA), located on the medial side of the vestibule. While the functions of the cochlea and the vestibular part of the inner ear are rather well studied, our knowledge of the function/s of the ES and ED remains limited and has intrigued scientists for centuries. Earlier studies have supported several theories, such as being an immune mediator, an aid in pressure regulation, related to the absorption of endolymph, and the production of endolymph.

 Otologic disorders, which affect both hearing and balance, such as Meniere’s disease (MD) and large vestibular aqueduct syndrome (LVAS), have been linked to dysfunction of the ES/ED. Studies of the human inner ear are fairly sparse. Research on the ES and ED have mainly been performed on animals, although both the anatomy and function may differ among various species.

This thesis aims to further investigate the anatomy and function of the human ES and ED with the two otologic disorders MD and LVAS in mind. To achieve this, we have used novel imaging techniques, such as super-resolution structured illumination microscopy (SR-SIM), micro-computerized tomography (micro-CT), and synchrotron radiation phase-contrast imaging (SR-PCI). The material used for imaging comes from different sources: human archival temporal bones from the Uppsala temporal bone collection; human fresh-frozen cadaveric bones from our collaborators at Western University, in London, Ontario, Canada; and fresh-frozen human ES harvested during vestibular schwannoma surgery after securing ethical permission.

The results of these studies describe the micro-anatomy of the VA, ED and ES down to a nanoscopic level. The discussion is based on the findings, relating them to earlier research with clinical implications regarding MD and LVAS.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 71
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1647
Keywords
Endolymphatic sac, endolymphatic duct, vestibular aqueduct, Meniere's disease, LVAS, micro-CT, synchrotron phase contrast imaging
National Category
Otorhinolaryngology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-406848 (URN)978-91-513-0901-9 (ISBN)
Public defence
2020-05-07, Enghoffsalen, Akademiska sjukhuset, Ing 50, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2020-04-16 Created: 2020-03-13 Last updated: 2020-05-19

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Kämpfe Nordström, CharlottaDanckwardt-Lillieström, NiklasLiu, WeiRask-Andersen, Helge

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