Ion transport mechanisms responsible for K+ secretion and the transepithelial voltage across marginal cells of stria vascularis in vitro

Wangemann, Philine; Liu, Jianzhong; Marcus, Daniel C.

doi:10.1016/0378-5955(95)00009-s

Cited by 235 publications

(188 citation statements)

References 40 publications

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“…Despite high levels of PMCA1 in the stria vascularis and interdental cells, abnormal localization of PMCA1 to hair cell apical surfaces, and the presence of PMCA4 in stereocilia, dfw 2J endolymph Ca 2+ concentrations are significantly lower than those of wild-type mice, suggesting that PMCA2 is necessary to maintain normal endolymph Ca 2+ levels. Thus, our findings indicate that, unlike potassium whose endolymph concentration is believed to be established by the stria vascularis (Konishi et al 1978;Wangemann et al 1995), Ca 2+ endolymph concentrations are maintained, at least in part, by inner and outer hair cells.…”

Section: Pmca2 and Endolymph Ca 2+mentioning

confidence: 84%

Low Endolymph Calcium Concentrations in deafwaddler2J Mice Suggest that PMCA2 Contributes to Endolymph Calcium Maintenance

Wood

Muchinsky

Filoteo

et al. 2004

JARO

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In vertebrates, transduction of sound into an electrochemical signal is carried out by hair cells that rely on calcium to perform specialized functions. The apical surfaces of hair cells are surrounded by endolymphatic fluid containing calcium at concentrations that must be maintained by active transport. The mechanism of this transport is unknown, but an ATPdependent pump is believed to participate. Mutation of the Atp2b2 gene that encodes plasma membrane calcium ATPase type 2 (PMCA2) produces the deaf, ataxic mouse: deafwaddler 2J (dfw 2J ). We hypothesized that PMCA2 might transport calcium into the endolymph and that dfw 2J mice would have low endolymph calcium concentrations, possibly contributing to their deafness and ataxia. First, using immunocytochemistry, we demonstrated that PMCA2 is present in control mice inner and outer hair cell stereocilia where it could pump calcium into the endolymph and that PMCA2 is absent in dfw 2J stereocilia. Second, using an aspirating microelectrode and calcium-sensitive fluorescent dye, we found that dfw 2J mice endolymph calcium concentrations are significantly lower than those of control mice. These findings suggest that PMCA2, located in hair cell stereocilia, contributes significantly to endolymph calcium maintenance.

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Section: Pmca2 and Endolymph Ca 2+mentioning

confidence: 84%

Low Endolymph Calcium Concentrations in deafwaddler2J Mice Suggest that PMCA2 Contributes to Endolymph Calcium Maintenance

Wood

Muchinsky

Filoteo

et al. 2004

JARO

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“…In turn, lateral wall structures, in particular, the stria vascularis, are critical in maintaining ion homeostasis of the endolymph (Offner et al 1987;Salt et al 1987;Wangemann 1995;Wangemann et al 1995;Takeuchi and Ando 1998). The presence of Na/K-ATPases and Na/K/Cl cotransporters in the fibrocytes of the spiral ligament suggest that the ligament also plays a key role in the maintenance of the ionic environment and the endocochlear potential (Schulte and Adams 1989;Spicer and Schulte 1996;Crouch et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Lateral Wall Histopathology and Endocochlear Potential in the Noise-Damaged Mouse Cochlea

Hirose

Liberman

2003

JARO - Journal of the Association for Research in Otolaryngolog

247

221

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Noise exposure damages the stria and spiral ligament and may contribute to noise-induced threshold shift by altering the endocochlear potential (EP). The aim of this study was to correlate lateral wall histopathology with changes in EP and ABR thresholds. CBA/CaJ mice were exposed to octave band (8-16 kHz) noise for 2 h at intensities ranging from 94 to 116 dB SPL and evaluated 0 h to 8 weeks postexposure. EP in control mice averaged 86 and 101 mV in apical and basal turns, respectively. The 94 dB exposures caused a 40 dB temporary threshold shift (TTS), and there was with no corresponding change in EP. The 112 and 116 dB exposures caused >60 dB threshold shifts at 24 h, and EP was transiently decreased, e.g., to 21 and 27 mV in apical and basal turns after 116 dB. By 1 week postexposure, EP returned to control values in all exposure groups, although those exposed to 112 or 116 dB showed large permanent threshold shifts (PTS). Cochleas were plastic-embedded and serialsectioned for light microscopic and ultrastructural analysis. Acute changes included degeneration of type II fibrocytes of the spiral ligament and strial edema. The strial swelling peaked at 24 h when significant EP recovery had taken place, suggesting that these changes reflect compensatory volume changes. In the chronic state, massive loss of type II fibrocytes and degeneration of strial intermediate and marginal cells was observed with drastic reduction in membrane surface area. The results suggest that EP shifts do not occur with TTS and also do not add significantly to PTS in the steady state. However, EP loss could contribute to acute threshold shifts that resolve to a PTS. EP recovery despite significant strial degeneration may be partly due to decreased transduction current caused by hair cell damage.

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“…Furosemide-induced declines in the EP are thought to be the result of the inhibition of NKCC in the basolateral membrane of the marginal cells in the stria vascularis (Sakaguchi et al 1998;Wangemann et al 1995). NKCC is an important protein that aides the active transport of sodium, potassium, and chloride into and out of cells.…”

Section: Fig 13mentioning

confidence: 99%

Chronic Reduction of Endocochlear Potential Reduces Auditory Nerve Activity: Further Confirmation of an Animal Model of Metabolic Presbyacusis

Lang

Jyothi

Smythe

et al. 2010

JARO

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Gerbils aged in quiet show a decline of the endocochlear potential (EP) and elevated auditory nerve compound action potential (CAP) thresholds. However, establishing a direct relationship between an age-related reduction in the EP and changes in the activities of primary auditory neurons is difficult owing to the complexity of age-related histological changes in the cochlea. To address this issue, we developed a young gerbil model of "metabolic" presbyacusis that uses an osmotic pump to deliver furosemide into the round window niche for 7 days, resulting in a chronically reduced EP. In this model, the only major histopathologic changes were restricted to the hook region of the cochlea and consisted of loss of strial intermediate cells and massive edema in the lateral wall. The morphological and physiological evidence suggests that the cochlea can adapt to furosemide application over time. The morphology of spiral ganglion cells and hair cells appeared normal throughout the cochlea. CAP responses and EP values in this model are similar to those of quiet-aged ears. The spontaneous activity of single auditory fibers (n= 188) was assessed in 15 young gerbils treated with furosemide for 7 days. The percentage of recorded low-spontaneous rate (SR) fibers at characteristic frequencies (CFs)≥6 kHz was significantly lower in furosemide-treated than in control ears. Recovery function tests of CAP responses after prior stimulation also showed a decline in activity of the low-SR population with CFs≥6 kHz in the treated cochleas. A similar loss in the activity of low-SR fiber has been previously shown in quiet-aged gerbils. These results suggest that dysfunction of the cochlear lateral wall and subsequent chronic reduction in the EP can directly affect the activity patterns of primary auditory neurons in a manner similar to that seen in aged gerbils.

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Ion transport mechanisms responsible for K+ secretion and the transepithelial voltage across marginal cells of stria vascularis in vitro

Cited by 235 publications

References 40 publications

Low Endolymph Calcium Concentrations in deafwaddler2J Mice Suggest that PMCA2 Contributes to Endolymph Calcium Maintenance

Low Endolymph Calcium Concentrations in deafwaddler2J Mice Suggest that PMCA2 Contributes to Endolymph Calcium Maintenance

Lateral Wall Histopathology and Endocochlear Potential in the Noise-Damaged Mouse Cochlea

Chronic Reduction of Endocochlear Potential Reduces Auditory Nerve Activity: Further Confirmation of an Animal Model of Metabolic Presbyacusis

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