Homeostatic Mechanisms in the Cochlea

Wangemann, Philine; Schacht, Jochen

doi:10.1007/978-1-4612-0757-3_3

Cited by 175 publications

(163 citation statements)

References 248 publications

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“…In the present study, the endolymphatic K + in both mouse strains was lower than the mean commonly taken to represent mammalian endolymph, e.g., 150-160 mM (Wangemann and Schacht 1996). We also previously found relatively low [K + ] e (113 mM) in wild-type mice of a mixed 129Sv and C57BL/6 genetic background in another study from our lab (Marcus et al 2002).…”

Section: Discussionsupporting

confidence: 54%

Age-Related Changes in Cochlear Endolymphatic Potassium and Potential in CD-1 and CBA/CaJ Mice

Marcus

2003

JARO - Journal of the Association for Research in Otolaryngolog

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The CD-1 mouse strain is known to have early onset of hearing loss that is progressive with aging. We sought to determine whether a disturbance of K + homeostasis and pathological changes in the cochlear lateral wall were involved in the age-related hearing loss (AHL) of CD-1 as compared to the CBA/CaJ strain which has minimal AHL. In the present study, the endocochlear potential (EP) and endolymphatic K + concentration ([K + ] e ) were measured in both strains of mice with double-barrel microelectrodes at ''young'' (1-2 mo) and ''old'' (5-9 mo) ages. CBA/ CaJ mice displayed no changes with aging in EP and [K + ] e of the basal turn. In the apical turn, there was a small positive shift of the EP (10 mV) with aging under both normoxic and acute anoxic conditions ()EP), without any change of [K + ] e . Further, there were no obvious pathological changes in the lateral wall of CBA/CaJ mice. By contrast, old CD-1 mice displayed a significantly reduced [K + ] e by 30% in both basal and apical turns with no significant changes in normoxic EP. The )EP in the apical turn was significantly reduced in magnitude by 6 mV. A severe loss of cells with aging was observed in the region of type IV fibrocytes of the apical and basal turns and of type II fibrocytes in the basal turn. A complete degeneration of organ of Corti was also observed at the basal turn of old CD-1 mice, as well as a basalward decline of spiral ganglion neuron density. The pathological changes in spiral ligament of CD-1 mice were similar to those of an inbred mouse strain C57BL/6J that expresses an AHL gene (ahl) and might be a primary etiology of AHL of CD-1 mice. These findings have ramifications for our understanding of AHL and for interpretation of genetic mutations in a CD-1 background.

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Section: Discussionsupporting

confidence: 54%

Age-Related Changes in Cochlear Endolymphatic Potassium and Potential in CD-1 and CBA/CaJ Mice

Marcus

2003

JARO - Journal of the Association for Research in Otolaryngolog

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“…6 i, l, and m). Both cell types are involved in producing the endolymph and therefore the endocochlear potential (7)(8)(9). This expression pattern is in keeping with the reduced stria vascularis and the rounding up and loss of the cytoplasmic processes of its marginal cells in Va/Va and Va/ϩ mice (2) and with the reduced endocochlear potentials of the Va J mutants (1,3).…”

Section: Resultsmentioning

confidence: 62%

The varitint-waddler (Va) deafness mutation in TRPML3 generates constitutive, inward rectifying currents and causes cell degeneration

Nagata¹,

Zheng

Madathany³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

118

141

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Varitint-waddler (Va andVaA very common cause of deafness is the loss of hair cells, which degenerate because of environmental factors or genetic mutations. Varitint-waddler (Va) mice have a mutation that causes an alanine-to-proline substitution (A419P) in the fifth transmembrane domain of TRPML3, a presumed ion channel. A second allele, Va J , contains the A419P mutation in cis to an I362T mutation (1). The earliest sign of inner ear damage in Va mice is hair cell degeneration, which begins in embryogenesis as hair cells differentiate and continues postnatally. During degeneration, the hair cells bulge out of the apical side of the epithelium and become extruded. Eventually these mice also develop abnormalities in supporting cells, in the tectorial membrane, and in the stria vascularis and in the endocochlear potential that they help generate. The defects of Va J mice are similar although less severe, suggesting that the mutation I362T attenuates the effects of A419P (1-3). A comprehensive examination of TRPML3 expression in inner ear has not been published. Expression of TRPML3 protein in hair cells was suggested by immunocytochemical methods, although results for other inner ear cell types were not reported (1).Mutations in two other TRP channels, Drosophila TRP and human TRPML1 (mutations in which cause mucolipidosis type IV), are associated with degeneration of the retina. In both cases, the channels seem necessary for cellular viability, because recessive, loss-of-function mutations cause degeneration (4, 5).By contrast, the Va and Va J mutations in TRPML3 are semidominant, although it remains unclear whether this is due to gain-of-function, haploinsufficiency, or dominant-negative effects (1, 6). ResultsWe first established which cells expressed TRPML3 in the inner ear of wild-type mice. In situ hybridization on mouse inner ear using probes from two nonoverlapping regions of TRPML3 mRNA gave identical results [ Fig. 1 and supporting information (SI) Fig. 6]. TRPML3 mRNA was most abundant in the marginal cells of the cochlear stria vascularis and the dark cells of the vestibule (Fig. 1 i, l, and m and SI Fig. 6 i, l, and m). Both cell types are involved in producing the endolymph and therefore the endocochlear potential (7-9). This expression pattern is in keeping with the reduced stria vascularis and the rounding up and loss of the cytoplasmic processes of its marginal cells in Va/Va and Va/ϩ mice (2) and with the reduced endocochlear potentials of the Va J mutants (1, 3).In addition, other cells that line the cochlear scala media and the connected vestibular endolymphatic spaces expressed TRPML3 mRNA, including (i) supporting cells at the marginal part of the lesser epithelial ridge (Hensen and Claudius cells), which in Va and Va J mice (homozygotes and heterozygotes) appear undifferentiated or degenerate ( Fig. 1i and SI Fig. 6i); (ii) cells of the spiral limbus that produce the tectorial membrane, which in Va mice develops abnormally and fails to attach to the reticular lamina ( Fig. 1i and SI Fig. 6i...

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“…An understanding of molecular mechanisms of cochlear homeostasis, fluid, and ion balance in the inner ear has been advanced significantly (e.g. Wangemann and Schacht, 1996). Genes responsible for deafness have been identified, along with their phenotypes, and appropriate mouse models are available (e.g.…”

Section: Introductionmentioning

confidence: 99%

Basilar Membrane and Tectorial Membrane Stiffness in the CBA/CaJ Mouse

Teudt

Richter

2014

JARO

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The mouse has become an important animal model in understanding cochlear function. Structures, such as the tectorial membrane or hair cells, have been changed by gene manipulation, and the resulting effect on cochlear function has been studied. To contrast those findings, physical properties of the basilar membrane (BM) and tectorial membrane (TM) in mice without gene mutation are of great importance. Using the hemicochlea of CBA/CaJ mice, we have demonstrated that tectorial membrane (TM) and basilar membrane (BM) revealed a stiffness gradient along the cochlea. While a simple spring mass resonator predicts the change in the characteristic frequency of the BM, the spring mass model does not predict the frequency change along the TM. Plateau stiffness values of the TM were 0.6±0.5, 0.2± 0.1, and 0.09±0.09 N/m for the basal, middle, and upper turns, respectively. The BM plateau stiffness values were 3.7±2.2, 1.2±1.2, and 0.5±0.5 N/m for the basal, middle, and upper turns, respectively. Estimations of the TM Young's modulus (in kPa) revealed 24.3±25.2 for the basal turns, 5.1±4.5 for the middle turns, and 1.9±1.6 for the apical turns. Young's modulus determined at the BM pectinate zone was 76.8±72, 23.9±30.6, and 9.4±6.2 kPa for the basal, middle, and apical turns, respectively. The reported stiffness values of the CBA/CaJ mouse TM and BM provide basic data for the physical properties of its organ of Corti.

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Homeostatic Mechanisms in the Cochlea

Cited by 175 publications

References 248 publications

Age-Related Changes in Cochlear Endolymphatic Potassium and Potential in CD-1 and CBA/CaJ Mice

Age-Related Changes in Cochlear Endolymphatic Potassium and Potential in CD-1 and CBA/CaJ Mice

The varitint-waddler (Va) deafness mutation in TRPML3 generates constitutive, inward rectifying currents and causes cell degeneration

Basilar Membrane and Tectorial Membrane Stiffness in the CBA/CaJ Mouse

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