\u201cReversed polarization\u201d of Na/K-ATPase\u2014a sign of inverted transport in the human endolymphatic sac: a super-resolution structured illumination microscopy (SR-SIM) study

Abstract

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.