Na-K-Cl cotransporter expression in the developing and senescent gerbil cochlea

Sakaguchi, Nobuki; Crouch, James J.; Lytle, Christian; Schulte, Bradley A.

doi:10.1016/s0378-5955(98)00022-7

Cited by 79 publications

(73 citation statements)

References 53 publications

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“…3A). To exclude the possible direct effects of loop diuretics on supporting cells, we confirmed that the Na + -K + -2Cl − ion cotransporter (NKCC1), a primary target of loop diuretics (MacVicar et al 2002), is not expressed in the nontraumatized (Crouch et al 1997;Sakaguchi et al 1998) or traumatized organ of Corti (Fig. 3B, B').…”

Section: Ohc Apoptosis and Dcs Swelling Within The Sensory Epitheliummentioning

confidence: 61%

How to Bury the Dead: Elimination of Apoptotic Hair Cells from the Hearing Organ of the Mouse

Anttonen

Belevich

Kirjavainen

et al. 2014

JARO

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Hair cell death is a major cause of hearing impairment. Preservation of surface barrier upon hair cell loss is critical to prevent leakage of potassium-rich endolymph into the organ of Corti and to prevent expansion of cellular damage. Understanding of wound healing in this cytoarchitecturally complex organ requires ultrastructural 3D visualization. Powered by the serial block-face scanning electron microscopy, we penetrate into the cell biological mechanisms in the acute response of outer hair cells and glial-like Deiters' cells to ototoxic trauma in vivo. We show that Deiters' cells function as phagocytes. Upon trauma, their phalangeal processes swell and the resulting close cellular contacts allow engulfment of apoptotic cell debris. Apical domains of dying hair cells are eliminated from the inner ear sensory epithelia, an event thought to depend on supporting cells' actomyosin contractile activity. We show that in the case of apoptotic outer hair cells of the organ of Corti, elimination of their apices is preceded by strong cell body shrinkage, emphasizing the role of the dying cell itself in the cleavage. Our data reveal that the resealing of epithelial surface by junctional extensions of Deiters' cells is dynamically reinforced by newly polymerized F-actin belts. By analyzing Cdc42-inactivated Deiters' cells with defects in actin dynamics and surface closure, we show that compromised barrier integrity shifts hair cell death from apoptosis to necrosis and leads to expanded hair cell and nerve fiber damage. Our results have implications concerning therapeutic protective and regenerative interventions, because both interventions should maintain barrier integrity.

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Section: Ohc Apoptosis and Dcs Swelling Within The Sensory Epitheliummentioning

confidence: 61%

How to Bury the Dead: Elimination of Apoptotic Hair Cells from the Hearing Organ of the Mouse

Anttonen

Belevich

Kirjavainen

et al. 2014

JARO

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“…Animal models of age-related hearing loss demonstrate progressive alteration of biochemical and structural integrity of the cochlear lateral wall, including reduction in expression and activity of Na,K-ATPase, reduction in expression of NKCC1, involution and atrophy of the stria vascularis, degeneration of spiral ligament fibrocytes, segmental degeneration of capillary vasculature, and decline in EP associated with such changes (Gratton et al 1996Hequembourg and Liberman 2001;McGuirt and Schulte 1994;Sakaguchi et al 1998;Schulte and Adams 1989;Schulte and Schmiedt 1992;Schulte and Steel 1994;Spicer et al 1997). …”

Section: Discussionmentioning

confidence: 99%

“…Besides a 1 -Na,K-ATPase, which is expressed in the mammalian body ubiquitously, a 2 -Na,K-ATPase and NKCC1 are expressed in a predominantly cell-specific manner, suggesting distinct cellular function (Kaplan et al 1996;Lingrel et al 2003). The decline in activity of the Na,K-ATPase isoforms within the inner ear has been shown to correlate well with the decline in EP with aging (Gratton et al 1996;Gratton et al 1997;Sakaguchi et al 1998). In addition, a reduction in the level of NKCC1 expression, as seen in heterozygote mutant NKCC1 +/_ mice, results in elevated hearing threshold relative to wildtype littermates (Flagella et al 1999).…”

Section: Introductionmentioning

confidence: 98%

Conservation of Hearing by Simultaneous Mutation of Na,K-ATPase and NKCC1

Diaz

Vázquez

Dou

et al. 2007

JARO

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Although drug-induced and age-related hearing losses are frequent otologic problems affecting millions of people, their underlying mechanisms remain uncertain. The inner ear is exclusively endowed with a positive endocochlear potential (EP) that serves as the main driving force for the generation of receptor potential in hair cells to confer hearing. Deterioration of EP leads to hearing loss or deafness. The generation of EP relies on the activity of many ion transporters to establish active potassium (K + ) cycling within the inner ear, including K + channels, the Na-K-2Cl co-transporter (NKCC1), and the a 1 and a 2 isoforms of Na,K-ATPase. We show that heterozygous deletion of either NKCC1, a 1 -Na,K-ATPase, or a 2 -Na,K-ATPase independently results in progressive, age-dependent hearing loss with minimal alteration in cochlear morphology. Double heterozygote deletion of NKCC1 with a 1 -Na,K-ATPase also shows a progressive, though delayed, age-dependent hearing loss. Remarkably, double heterozygote deletion of NKCC1 with a 2 -Na,K-ATPase demonstrates a striking preservation of hearing threshold both initially and with age. Measurements of the EP confirm the anticipated drop in potential for genotypes that demonstrate age-dependent hearing loss. The EP generated by the NKCC1 + a 2 -Na,K-ATPase double heterozygote, however, is maintained at a level comparable to that of the control condition, suggesting a potential advantage in this combination of ion transporter modification. These observations provide insight into the detailed mechanisms of EP generation, and results of combination-knockout experiments may have important implications in the future treatment of drug-induced and age-related hearing losses.

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“…The K ϩ concentration in endolymph is high and the Na ϩ concentration is low, resulting in a high resting endocochlear potential. The maintenance of high K ϩ concentration in endolymph after acoustic signal transduction requires rapid recycling of K ϩ into the endolymph (35,36). Indeed, at least six of the many proteins associated with deafness in humans and mice are probably involved in K ϩ recycling (37), including the KCNQ4 K ϩ channel, which is mutated in one type of dominant progressive hearing loss (36).…”

Section: Discussionmentioning

confidence: 99%

Impaired Hearing in Mice Lacking Aquaporin-4 Water Channels

Verkman

2001

Journal of Biological Chemistry

239

154

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A role for aquaporins (AQPs) in hearing has been suggested from the specific expression of aquaporins in inner ear and the need for precise volume regulation in epithelial cells involved in acoustic signal transduction. Using mice deficient in selected aquaporins as controls, we localized AQP1 in fibrocytes in the spiral ligament and AQP4 in supporting epithelial cells (Hensen's, Claudius, and inner sulcus cells) in the organ of Corti. To determine whether aquaporins play a role in hearing, auditory brain stem response (ABR) thresholds were compared in wild-type mice and transgenic null mice lacking (individually) AQP1, AQP3, AQP4, and AQP5. In 4 -5-week-old mice in a CD1 genetic background, ABR thresholds in response to a click stimulus were remarkably increased by >12 db in AQP4 null mice compared with wild-type mice (p < 0.001), whereas ABR thresholds were not affected by AQP1, AQP3, or AQP5 deletion. In a C57/bl6 background, nearly all AQP4 null mice were deaf, whereas ABRs could be elicited in wildtype controls. ABRs in AQP4 null CD1 mice measured in response to tone bursts (4 -20 kHz) indicated a frequency-independent hearing deficit. Light microscopy showed no differences in cochlear morphology of wildtype versus AQP4 null mice. These results provide the first direct evidence that an aquaporin water channel plays a role in hearing. AQP4 may facilitate rapid osmotic equilibration in epithelial cells in the organ of Corti, which are subject to large K ؉ fluxes during mechano-electric signal transduction.The aquaporins (AQPs) 1 are a family of small integral membrane proteins that function as water transporters. Phenotype analysis of mice lacking aquaporins has indicated that they play a physiological role in the kidney, central nervous system, gastrointestinal system, and exocrine glands (reviewed in Ref. 1). Mice lacking AQP1, AQP2, or AQP3 manifest nephrogenic diabetes insipidus with defective urinary concentrating ability (2-4), mice lacking AQP4 have altered brain water balance in response to injury (5), and mice lacking AQP5 have defective saliva secretion (6). In humans, mutations in AQP2 cause the autosomal form of hereditary nephrogenic diabetes insipidus (7). Phenotype studies have also shown the tissue-specific expression of an aquaporin does not prove its physiological importance. For example, mice lacking AQP4 in gastric parietal cells and skeletal muscle have unimpaired stomach acid secretion (8) and skeletal muscle function (9). The data from aquaporin null mice suggest that aquaporins are functionally important in tissues carrying out rapid near isosmolar fluid transport or passive water transport driven by osmotic gradients (1).Several aquaporins have been localized in the mammalian inner ear and have been proposed to play a role in hearing. Reverse transcriptase polymerase chain reaction analysis of dissected rat inner ear showed diffuse AQP1 transcript expression, specific expression of AQP2, AQP3, and AQP4 in the endolymphatic sac, and expression of AQP5 in the organ of Corti and Reissn...

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Na-K-Cl cotransporter expression in the developing and senescent gerbil cochlea

Cited by 79 publications

References 53 publications

How to Bury the Dead: Elimination of Apoptotic Hair Cells from the Hearing Organ of the Mouse

How to Bury the Dead: Elimination of Apoptotic Hair Cells from the Hearing Organ of the Mouse

Conservation of Hearing by Simultaneous Mutation of Na,K-ATPase and NKCC1

Impaired Hearing in Mice Lacking Aquaporin-4 Water Channels

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