Functional and Molecular Expression of Epithelial Sodium Channels in Cultured Human Endolymphatic Sac Epithelial Cells

Kim, Sung Huhn; Park, Hun Yi; Choi, Hyun Seung; Chung, Hyun Pil; Choi, Jae Young

doi:10.1097/mao.0b013e31819a8e0e

Cited by 30 publications

(27 citation statements)

References 28 publications

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“…The negative transepithelial potential found in the prenatal endolymphatic sac (Fig. 4D) is consistent with electrogenic Na + absorption mediated by a channel such as ENaC, which has been found to be expressed in the endolymphatic sac [33]. Whether ENaC or other ion transporters mediate fluid absorption in the endolymphatic sac is beyond the scope of the present study.…”

Section: Discussionsupporting

confidence: 86%

Endolymphatic Na+ and K+ Concentrations during Cochlear Growth and Enlargement in Mice Lacking Slc26a4/pendrin

Zhou

Marcus

et al. 2013

PLoS ONE

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Slc26a4 Δ/Δ mice are deaf, develop an enlarged membranous labyrinth, and thereby largely resemble the human phenotype where mutations of SLC26A4 cause an enlarged vestibular aqueduct and sensorineural hearing loss. The enlargement is likely caused by abnormal ion and fluid transport during the time of embryonic development, however, neither the mechanisms of ion transport nor the ionic composition of the luminal fluid during this time of development are known. Here we determine the ionic composition of inner ear fluids at the time at which the enlargement develops and the onset of expression of selected ion transporters. Concentrations of Na+ and K+ were measured with double-barreled ion-selective electrodes in the cochlea and the endolymphatic sac of Slc26a4 Δ/+, which develop normal hearing, and of Slc26a4 Δ/Δ mice, which fail to develop hearing. The expression of specific ion transporters was examined by quantitative RT-PCR and immunohistochemistry. High Na+ (∼141 mM) and low K+ concentrations (∼11 mM) were found at embryonic day (E) 16.5 in cochlear endolymph of Slc26a4 Δ/+ and Slc26a4 Δ/Δ mice. Shortly before birth the K+ concentration began to rise. Immediately after birth (postnatal day 0), the Na+ and K+ concentrations in cochlear endolymph were each ∼80 mM. In Slc26a4 Δ/Δ mice, the rise in the K+ concentration occurred with a ∼3 day delay. K+ concentrations were also found to be low (∼15 mM) in the embryonic endolymphatic sac. The onset of expression of the K+ channel KCNQ1 and the Na+/2Cl−/K+ cotransporter SLC12A2 occurred in the cochlea at E19.5 in Slc26a4 Δ/+ and Slc26a4 Δ/Δ mice. These data demonstrate that endolymph, at the time at which the enlargement develops, is a Na+-rich fluid, which transitions into a K+-rich fluid before birth. The data suggest that the endolymphatic enlargement caused by a loss of Slc26a4 is a consequence of disrupted Na+ transport.

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Section: Discussionsupporting

confidence: 86%

Endolymphatic Na+ and K+ Concentrations during Cochlear Growth and Enlargement in Mice Lacking Slc26a4/pendrin

Zhou

Marcus

et al. 2013

PLoS ONE

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“…Further, a cooperative model of Na + absorption involving both major cell types has been proposed (Kim and Wangemann, 2010). Many ion channels and transporters potentially involved in Na + transport in the endolymphatic sac epithelial cells were reported, including a nonselective cation channel (Miyashita et al, 2001; Wu and Mori, 1999), low-amiloride-affinity Na + channel (LAASC) (Mori and Wu, 1996), α-,β-and γ-subunits of ENaC (Kim et al, 2009b), NHE at the apical membrane (Son et al, 2009), NKCC1 and 2 (Akiyama et al, 2007), and Na + ,K + -ATPase at the basolateral membrane (Mizukoshi et al, 1988). …”

Section: Endolymphatic Sacmentioning

confidence: 99%

“…The nonselective cation channel was sensitive to cytosolic [Ca 2+ ] and was voltage-dependent (Miyashita et al, 2001). ENaC and NHE were identified in cultured human endolymphatic epithelial cells by RT-PCR and by measurement of transepithelial current and its sensitivity to NHE inhibitors in confluent monlayers (Kim et al, 2009b; Son et al, 2009). Among the three isoforms of NHEs identified by RT-PCR (NHE1,2,3) in cultured human endolymphatic sac epithelial cells, NHE2 are the most likely to regulate pH and Na + concentration of luminal fluid of endolymphatic sac, although evidence for the involvement of NHE1 (a basolateral NHE isoform in other epithelia) was also found (Son et al, 2009).…”

Section: Endolymphatic Sacmentioning

confidence: 99%

Regulation of sodium transport in the inner ear

Kim

Marcus

2011

Hearing Research

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Na+ concentrations in endolymph must be controlled to maintain hair cell function since the transduction channels of hair cells are cation-permeable, but not K+-selective. Flooding or fluctuations of the hair cell cytosol with Na+ would be expected to lead to cellular dysfunction, hearing loss and vertigo. This review briefly describes cellular mechanisms known to be responsible for Na+homeostasis in each compartment of the inner ear, including the cochlea, saccule, semicircular canals and endolymphatic sac. The influx of Na+into endolymph of each of the organs is likely via passive diffusion, but these pathways have not yet been identified or characterized. Na+ absorption is controlled by gate -keeper channels in the apical (endolymphatic) membrane of the transporting cells. Highly Na+-selective epithelial sodium channels (ENaC) control absorption by Reissner’s membrane, saccular extramacular epithelium, semicircular canal duct epithelium and endolymphatic sac. ENaC activity is controlled by a number of signal pathways, but most notably by genomic regulation of channel numbers in the membrane via glucocorticoid signaling. Nonselective cation channels in the apical membrane of outer sulcus epithelial cells and vestibular transitional cells mediate Na+ and parasensory K+ absorption. The K+-mediated transduction current in hair cells is also accompanied by a Na+ flux since the transduction channels are nonselective cation channels. Cation absorption by all of these cells is regulated by extracellular ATP via apical nonselective cation channels (P2X receptors). The heterogeneous population of epithelial cells in the endolymphatic sac is thought to have multiple absorptive pathways for Na+ with regulatory pathways that include glucocorticoids and purinergic agonists.

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“…Also, a gene polymorphism in adducin, which increases Na + ,K + -ATPase function, is increased in Meniere's patients [90]. ENac is also suppressed in the endolymphatic sac by inflammation [91], suggesting reduced movement of Na + out of the endolymph may increase hydrops. Salicylates downregulate cochlear aquaporin 6, which suggests a link between the hearing loss and tinnitus seen with nonsteroidal anti-inflammatories [92].…”

Section: Disorders Of Homeostasismentioning

confidence: 99%

Ion homeostasis in the ear: mechanisms, maladies, and management

Trune

2010

Current Opinion in Otolaryngology & Head and Neck Surgery

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Purpose of Review-Describe ion and water homeostatic mechanisms in the inner ear, how they are compromised in hearing disorders, and what treatments are employed to restore auditory function.Recent Findings-The ion and water transport functions in the inner ear help maintain the proper endolymph K + concentration required for hair cell function. Gene defects and idiopathic alterations in these transport functions cause hearing loss, but often the underlying cause is unknown. Current therapies largely involve glucocorticoid treatment, although the mechanisms of restoration are often undeterminable. Recent studies of these ion homeostatic functions in the ear are characterizing their cellular and molecular control. It is anticipated that future management of these hearing disorders will be more targeted to the cellular processes involved and improve the likelihood of hearing recovery.Summary-A better understanding of the ion homeostatic processes in the ear will permit more effective management of their associated hearing disorders. Sufficient insight into many homeostatic hearing disorders has now been attained to usher in a new era of better therapies and improved clinical outcomes.

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Functional and Molecular Expression of Epithelial Sodium Channels in Cultured Human Endolymphatic Sac Epithelial Cells

Cited by 30 publications

References 28 publications

Endolymphatic Na+ and K+ Concentrations during Cochlear Growth and Enlargement in Mice Lacking Slc26a4/pendrin

Endolymphatic Na+ and K+ Concentrations during Cochlear Growth and Enlargement in Mice Lacking Slc26a4/pendrin

Regulation of sodium transport in the inner ear

Ion homeostasis in the ear: mechanisms, maladies, and management

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