Slc26a7 Chloride Channel Activity and Localization in Mouse Reissner’s Membrane Epithelium

Abstract

Several members of the SLC26 gene family have highly-restricted expression patterns in the auditory and vestibular periphery and mutations in mice of at least two of these (SLC26A4 and SLC26A5) lead to deficits in hearing and/or balance. A previous report pointed to SLC26A7 as a candidate gene important for cochlear function. In the present study, inner ears were assayed by immunostaining for Slc26a7 in neonatal and adult mice. Slc26a7 was detected in the basolateral membrane of Reissner’s membrane epithelial cells but not neighboring cells, with an onset of expression at P5; gene knockout resulted in the absence of protein expression in Reissner’s membrane. Whole-cell patch clamp recordings revealed anion currents and conductances that were elevated for NO3 − over Cl− and inhibited by I− and NPPB. Elevated NO3 − currents were absent in Slc26a7 knockout mice. There were, however, no major changes to hearing (auditory brainstem response) of knockout mice during early adult life under constitutive and noise exposure conditions. The lack of Slc26a7 protein expression found in the wild-type vestibular labyrinth was consistent with the observation of normal balance. We conclude that SLC26A7 participates in Cl− transport in Reissner’s membrane epithelial cells, but that either other anion pathways, such as ClC-2, possibly substitute satisfactorily under the conditions tested or that Cl− conductance in these cells is not critical to cochlear function. The involvement of SLC26A7 in cellular pH regulation in other epithelial cells leaves open the possibility that SLC26A7 is needed in Reissner’s membrane cells during local perturbations of pH.

Overlapping expression of anion exchangers in the cochlea of a non-human primate suggests functional compensation

“…Although Slc26a7 KO mice suffer distal renal tubular acidosis (dRTA) (Xu et al, 2009), dRTA-related mutations in SLC26A7 have not been reported in humans. In the mouse cochlea, SLC26A7 expression has been reported in Reissner's membrane (Kim et al, 2014). In the common marmoset cochlea, SLC26A7 expression was observed in the outer hair cells and spiral ganglion neurons (Fig.…”

Fgf10 is required for specification of non-sensory regions of the cochlear epithelium

“…It consists of an inner, epithelial layer facing the endolymph of the scala media and an outer mesothelial layer facing the perilymph of the scala vestibuli. Its function is to help maintain the distinct ionic compositions of endolymph and perilymph (Kim et al, 2014; Kim and Marcus, 2011) as well as to propagate traveling waves that play a role in otoacoustic emissions (Reichenbach et al, 2012). The genetic networks required for Reissner’s membrane development are unexplored.…”

The unique ion permeability profile of cochlear fibrocytes and its contribution to establishing their positive resting membrane potential

“…1). The mechanism underlying the reduction in the EP for a low Cl − solution remains uncertain, but may involve outer sulcus cells and/or Reissner's membrane epithelial cells, both of which are exposed to the perilymph and express Cl − channels or transporters [18,31]. These cells constitute the boundary between perilymph and endolymph and they are believed to contribute to the EP.…”