KCNJ10 (Kir4.1) potassium channel knockout  abolishes endocochlear potential

Marcus, Daniel C.; Wu, Tao; Wangemann, Philine; Kofuji, Paulo

doi:10.1152/ajpcell.00312.2001

Cited by 296 publications

(265 citation statements)

References 29 publications

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“…They then diffuse into strial intermediate cells. The final step in K + recycling is the actual generation of the EP, when K + ions are released from the intermediate cells into the intrastrial space via the Kcnj10 K + channel [8,9]. This K + ion recycling pathway is one of the mechanisms that maintains the EP and ion homeostasis in the endolymph [3,4,10].…”

Section: Introductionmentioning

confidence: 99%

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Liu

Chen

et al. 2016

PLoS ONE

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Cochlear hair cells and the stria vascularis are critical for normal hearing. Hair cells transduce mechanical stimuli into electrical signals, whereas the stria is responsible for generating the endocochlear potential (EP), which is the driving force for hair cell mechanotransduction. We questioned whether hair cells and the stria interdepend for survival by using two mouse models. Atoh1 conditional knockout mice, which lose all hair cells within four weeks after birth, were used to determine whether the absence of hair cells would affect function and survival of stria. We showed that stria morphology and EP remained normal for long time despite a complete loss of all hair cells. We then used a mouse model that has an abnormal stria morphology and function due to mutation of the Mitf gene to determine whether hair cells are able to survive and transduce sound signals without a normal electrochemical environment in the endolymph. A strial defect, reflected by missing intermediate cells in the stria and by reduction of EP, led to systematic outer hair cell death from the base to the apex after postnatal day 18. However, an 18-mV EP was sufficient for outer hair cell survival. Surprisingly, inner hair cell survival was less vulnerable to reduction of the EP. Our studies show that normal function of the stria is essential for adult outer hair cell survival, while the survival and normal function of the stria vascularis do not depend on functional hair cells.

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Section: Introductionmentioning

confidence: 99%

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Liu

Chen

et al. 2016

PLoS ONE

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“…The EP is reliant on the function of lateral wall tissues as well as the magnitude of the ion conductance in tissues lining the scala media. The EP is thought to be the result of the large positive potential generated in the stria vascularis [32]. A decrease in tissueresistive pathways would be expected to cause a reduction in the EP [33].…”

Section: Discussionmentioning

confidence: 99%

Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea

Telang

Paramananthasivam

Vlajkovic

et al. 2010

Purinergic Signalling

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Extracellular adenosine triphosphate (ATP) has profound effects on the cochlea, including an effect on the regulation of the endocochlear potential (EP). Noise-induced release of ATP into the endolymph activates a shunt conductance mediated by P2X 2 receptors in tissues lining the endolymphatic compartment, which reduces the EP and, consequentially, hearing sensitivity. This may be a mechanism of adaptation or protection from high sound levels. As inaction of such a process could contribute to hearing loss, this study examined whether the action of ATP on EP changes with age and noise exposure in the mouse. The EP and the endolymphatic compartment resistance (CoPR) were measured in mice (CBA/CaJ) aged between 3 and 15 months. The EP and CoPR declined slightly with age with an associated small, but significant, reduction in auditory brainstem response thresholds. ATP (100-1,000 μM) microinjected into the endolymphatic compartment caused a dosedependent decline in EP correlated to a similar decrease in CoPR. This was blocked by pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate, consistent with a P2X 2 receptormediated shunt conductance. There was no substantial difference in the ATP response with age. Noise exposure (octave-band noise 80-100 decibels sound pressure level (dBSPL), 48 h) in young animals induced an upregulation of the P2X 2 receptor expression in the organ of Corti and spiral limbus, most noticeably with the 90-dB exposure. This did not occur in the aged animals except following exposure at 90 dBSPL. The EP response to ATP was muted in the noiseexposed aged animals except following the 90-dB exposure. These findings provide some evidence that the adaptive response of the cochlea to noise may be reduced in older animals, and it is speculated that this could increase their susceptibility to noise-induced injury.

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“…The strong expression of NHERFs at the basal barrier, which is formed by basal and intermediate cells, suggests that these factors are involved with regulating ion transport and homeostasis at regions where the endocochlear potential is generated by KCNJ10 (Kir 4.1) channels located in the intermediate cells (Marcus et al 2002;Gow et al 2004;Wangemann et al 2004;Spicer and Schulte 2005). NHERFs may spatially constrain Kir4.1 channels in intermediate cells.…”

Section: Discussionmentioning

confidence: 99%

Postnatal developmental expression of the PDZ scaffolds Na+-H+ exchanger regulatory factors 1 and 2 in the rat cochlea

et al. 2005

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Sensory transduction in the mammalian cochlea requires the maintenance of specialized fluid compartments with distinct ionic compositions. This is achieved by the concerted action of diverse ion channels and transporters, some of which can interact with the PDZ scaffolds, Na + -H + exchanger regulatory factors 1 and 2 (NHERF-1, NHERF-2). Here, we report that NHERF-1 and NHERF-2 are widely expressed in the rat cochlea, and that their expression is developmentally regulated. Reverse transcription/polymerase chain reaction (RT-PCR) and Western blotting initially confirmed the RNA and protein expression of NHERFs. We then performed immunohistochemistry on cochlea during various stages of postnatal development. Prior to the onset of hearing (P8), NHERF-1 immunolabeling was prominently polarized to the apical membrane of cells lining the endolymphatic compartment, including the stereocilia and cuticular plates of the inner and outer hair cells, marginal cells of the stria vascularis, Reissner's epithelia, and tectorial membrane. With maturation (P21, P70), NHERF-1 immunolabeling was reduced in the above structures, whereas labeling increased in the apical membrane of the interdental cells of the spiral limbus and the inner and outer sulcus cells, Hensen's cells, the inner and outer pillar cells, Deiters cells, the inner border cells, spiral ligament fibrocytes, and spiral ganglion neurons (particularly type II). NHERF-1 expression in strial basal and intermediate cells was persistent. NHERF-2 immunolabeling was similar to that for NHERF-1 during postnatal development, with the exception of expression in the synaptic regions beneath the outer hair cells. NHERF-1 and NHERF-2 co-localized with glial fibrillary acidic protein and vimentin in glia. The cochlear localization of NHERF scaffolds suggests that they play important roles in the developmental regulation of ion transport, homeostasis, and auditory neurotransmission.

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KCNJ10 (Kir4.1) potassium channel knockout abolishes endocochlear potential

Cited by 296 publications

References 29 publications

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea

Postnatal developmental expression of the PDZ scaffolds Na+-H+ exchanger regulatory factors 1 and 2 in the rat cochlea

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