Co-localisation of Kir4.1 and AQP4 in rat and human cochleae reveals a gap in water channel expression at the transduction sites of endocochlear K+ recycling routes

Abstract

Sensory transduction in the cochlea depends on perilymphatic-endolymphatic potassium (K(+)) recycling. It has been suggested that the epithelial supporting cells (SCs) of the cochlear duct may form the intracellular K(+) recycling pathway. Thus, they must be endowed with molecular mechanisms that facilitate K(+) uptake and release, along with concomitant osmotically driven water movements. As yet, no molecules have been described that would allow for volume-equilibrated transepithelial K(+) fluxes across the SCs. This study describes the subcellular co-localisation of the K(ir)4.1 K(+) channel (K(ir)4.1) and the aquaporin-4 water channel (AQP4) in SCs, on the basis of immunohistochemical double-labelling experiments in rat and human cochleae. The results of this study reveal the expression of K(ir)4.1 in the basal or basolateral membranes of the SCs in the sensory domain of the organ of Corti that are adjacent to hair cells and in the non-sensory domains of the inner and outer sulci that abut large extracellular fluid spaces. The SCs of the inner sulcus (interdental cells, inner sulcus cells) and the outer sulcus (Hensen's cells, outer sulcus cells) display the co-localisation of K(ir)4.1 and AQP4 expression. However, the SCs in the sensory domain of the organ of Corti reveal a gap in the expression of AQP4. The outer pillar cell is devoid of both K(ir)4.1 and AQP4. The subcellular co-localisation of K(ir)4.1 and AQP4 in the SCs of the cochlea described in this study resembles that of the astroglia of the central nervous system and the glial Mueller cells in the retina.

Zucker diabetic fatty rats, a model for type 2 diabetes, develop an inner ear dysfunction that can be attenuated by losartan treatment

“…The inwardly rectifying potassium channel K ir 4.1 has been found in the SV, spiral ganglion and, recently, also in the supporting cells (Hibino and Kurach 2006;Eckhard et al 2012). K ir 4.1 is abundantly localized in the IMCs.…”

Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

“…The pivotal role of strial melanocytes in the generation of the endocochlear potential is to secrete K + ions into the intrastrial space and hence they express the inward‐rectifying potassium channel KCNJ10 (also known as K ir 4.1, [MIM 602208]) (Ando and Takeuchi, 1999; Eckhard et al, 2012). In contrast to the potassium channels of the marginal cells, we did not observe any KCNJ10 expression in strial melanocytes up to the last stage we investigated, W18.…”

“…However, mutations in KCNJ10 itself have also been linked directly to Pendred syndrome (Yang et al, 2009). Interestingly, KCNJ10 has also been described in the root cells of the outer sulcus, both in the adult rodent and human cochlea (Jagger et al, 2010; Eckhard et al, 2012). Also, the expression pattern of KCNJ10 that we observed in the outer sulcus during cochlear development matches the known expression pattern of PENDRIN in the outer sulcus of the adult mouse cochlea (Royaux et al, 2003; Wangemann et al, 2004).…”

Expression of aquaporins in inner ear disease

“…A total of 47 studies examining AQP expression in the inner ear have been identified (Table ) . Of the 47 studies, 16 were in mice, 17 in rats, 17 in humans, and seven in other species.…”

“…In addition to mice, rats, and humans, there were five studies using guinea pigs, two studies using Mongolian gerbils, one study using zebrafish, and one study using leopard frogs . Of the studies conducted in humans, seven cases analyzed tissues obtained from the vestibular schwannoma, three cases analyzed tissues from the meningioma, and two cases analyzed the ES from patients with Meniere's disease who had undergone surgery . Two articles included autopsy studies, and three articles studied polymorphisms using blood samples .…”