Immunolocalization of calcium sensing and transport proteins in the murine endolymphatic sac indicates calciostatic functions within the inner ear

An exceptionally low calcium (Ca(2+)) concentration in the inner ear endolymph ([Ca(2+)](endolymph)) is crucial for proper auditory and vestibular function. The endolymphatic sac (ES) is believed to critically contribute to the maintenance of this low [Ca(2+)](endolymph). Here, we investigated the immunohistochemical localization of proteins that are presumably involved in the sensing and transport of extracellular Ca(2+) in the murine ES epithelium. Light microscopic and fluorescence immunolabeling in paraffin-embedded murine ES tissue sections (male C57BL/6 mice, 6–8 weeks old) demonstrated the presence of the calcium-sensing receptor CaSR, transient receptor potential cation channel subtypes TRPV5 and TRPV6, sarco/endoplasmic reticulum Ca(2+)-ATPases SERCA1 and SERCA2, Na(+)/Ca(2+) exchanger NCX2, and plasma membrane Ca(2+) ATPases PMCA1 and PMCA4 in ES epithelial cells. These proteins exhibited (i) membranous (apical or basolateral) or cytoplasmic localization patterns, (ii) a proximal-to-distal labeling gradient within the ES, and (iii) different distribution patterns among ES epithelial cell types (mitochondria-rich cells (MRCs) and ribosome-rich cells (RRCs)). Notably, in the inner ear membranous labyrinth, CaSR was exclusively localized in MRCs, suggesting a unique role of the ES epithelium in CaSR-mediated sensing and control of [Ca(2+)](endolymph). Structural loss of the distal ES, which is consistently observed in Meniere’s disease, may therefore critically disturb [Ca(2+)](endolymph) and contribute to the pathogenesis of Meniere’s disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00441-019-03062-2) contains supplementary material, which is available to authorized users.