Claudin expression in the rat endolymphatic duct and sac - first insights into regulation of the paracellular barrier by vasopressin

Abstract

Hearing and balance functions of the inner ear rely on the homeostasis of the endolymphatic fluid. When disturbed, pathologic endolymphatic hydrops evolves as observed in Menière’s disease. The molecular basis of inner ear fluid regulation across the endolymphatic epithelium is largely unknown. In this study we identified the specific expression of the tight junction (TJ) molecules Claudin 3, 4, 6, 7, 8, 10, and 16 in epithelial preparations of the rat inner ear endolymphatic duct (ED) and endolymphatic sac (ES) by high-throughput qPCR and immunofluorescence confocal microscopy. Further we showed that Claudin 4 in the ES is a target of arginine-vasopressin (AVP), a hormone elevated in Menière’s disease. Moreover, our transmission-electron microscopy (TEM) analysis revealed that the TJs of the ED were shallow and shorter compared to the TJ of the ES indicating facilitation of a paracellular fluid transport across the ED epithelium. The significant differences in the subcellular localization of the barrier-forming protein Claudin 3 between the ED and ES epithelium further support the TEM observations. Our results indicate a high relevance of Claudin 3 and Claudin 4 as important paracellular barrier molecules in the ED and ES epithelium with potential involvement in the pathophysiology of Menière’s disease.

Semicircular canal biomechanics in health and disease

“…The monolayer of extrasensory epithelial cells provides the electrochemical barrier between endolymph and perilymph (Köppl et al 2018). Compromise of the permeability or transport function of this epithelial barrier would be expected to result in loss of hair cell and sensory organ function (Kim and Marcus 2009; Kitajiri and Katsuno 2016; Runggaldier et al 2017; Sun and Wang 2015).…”

Mouse Models of Human Claudin-Associated Disorders: Benefits and Limitations

“…Claudin-16 is a pore forming claudin encoded by CLDN16 gene [16]. It is expressed in duodenum, jejunum, ileum, colon [90], in tooth germ [91], in salivary glands [92], and also has been found in the endolymphatic duct of the inner ear [93]. The by far highest expression has been found in the thick ascending limb (TAL) of the kidney [94].…”