Age-dependent changes in the expression of klotho protein, TRPV5 and TRPV6 in mouse inner ear

Takumida, Masaya; Ishibashi, Takuya; Hamamoto, Takao; Hirakawa, Katsuhiro; Anniko, Matti

doi:10.3109/00016480902725254

Cited by 40 publications

(27 citation statements)

References 18 publications

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“…Both TRPV5 and TRPV6 were shown to be expressed in the vestibular dark cells and in the epithelial cells of the semicircular canal duct epithelium (50,51). The abolished calcium reabsorbance of these channels leads to elevation in calcium levels in the endolymph to which the utricle is exposed.…”

Section: Initial Formation Of Giant Calcium Carbonate Stones In Slc26a4mentioning

confidence: 99%

Calcium Oxalate Stone Formation in the Inner Ear as a Result of an Slc26a4 Mutation

Dror

Politi

Shahin

et al. 2010

Journal of Biological Chemistry

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Calcium oxalate stone formation occurs under pathological conditions and accounts for more than 80% of all types of kidney stones. In the current study, we show for the first time that calcium oxalate stones are formed in the mouse inner ear of a genetic model for hearing loss and vestibular dysfunction in humans. The vestibular system within the inner ear is dependent on extracellular tiny calcium carbonate minerals for proper function. Thousands of these biominerals, known as otoconia, are associated with the utricle and saccule sensory maculae and are vital for mechanical stimulation of the sensory hair cells. We show that a missense mutation within the Slc26a4 gene abolishes the transport activity of its encoded protein, pendrin. As a consequence, dramatic changes in mineral composition, size, and shape occur within the utricle and saccule in a differential manner. Although abnormal giant carbonate minerals reside in the utricle at all ages, in the saccule, a gradual change in mineral composition leads to a formation of calcium oxalate in adult mice. By combining imaging and spectroscopy tools, we determined the profile of mineral composition and morphology at different time points. We propose a novel mechanism for the accumulation and aggregation of oxalate crystals in the inner ear.Biomineralization processes in the human body normally occur in a variety of different tissues, including bones, teeth, and otoconia within the vestibular system of the inner ear. The vestibular system is comprised of five sensory organs. Three cristae connected to semicircular canals are sensitive for angular movement, and the saccule and utricle are sensitive for linear acceleration and gravity. Otoconia are small highly dense calcitic minerals that associate exclusively with the saccule and utricle. Thousands of otoconia, partially embedded in a gelatinous matrix, are supported on the sensory epithelium and serve as an inertial mass that is critical for mechanical stimulation (1, 2) Movement of the otoconial layer through action of gravitational or inertial forces activate the underlying mechanosensory hair cells to generate action potentials that are transmitted to the brain.The biomineralization process, such as in otoconia formation, involves organic and inorganic components and results in biominerals that differ significantly in morphology and mechanical properties from similar synthetic or geological minerals (3, 4). Otoconia formation occurs outside the cells and therefore depends on secretion of the required assembly components into the endolymphatic spaces (5). Otoconia seeding in mice begins as early as embryonic day (E)14.5 4 and initiates extensive mineral growth, with the highest rate of calcification at E15-16 (6). By postnatal day (P)7, otoconia achieve their final size and are maintained at progressive ages with a low rate of calcium turnover (7). The main inorganic fraction of otoconia in birds and mammals is calcite (CaCO 3 ), a polymorph of calcium carbonate (2,8). The organic fraction of otoconia contains s...

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Section: Initial Formation Of Giant Calcium Carbonate Stones In Slc26a4mentioning

confidence: 99%

Calcium Oxalate Stone Formation in the Inner Ear as a Result of an Slc26a4 Mutation

Dror

Politi

Shahin

et al. 2010

Journal of Biological Chemistry

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“…Notably, TRPA1 has been suspected as a component of mechanotransduction channels at the hair bundles of sensory hair cells [55,56]. In SGNs, TRP receptors have been shown to be expressed in the cell body by immunohistochemistry: TRPV1-6 [57][58][59], TRPC1-7, more intensely in TRPC1 and TRPC3 [60,61], TRPM1, 2, 3, 6, 7, and 8 [62], TRPML1-3, TRPP2, 3, and 5 [63]. Modified expression of TRPV was reported following cochlear damage.…”

Section: Neuromodulation In Sgn/vgnmentioning

confidence: 99%

Purinergic signaling in cochleovestibular hair cells and afferent neurons

Ito

Dulon

2010

Purinergic Signalling

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Purinergic signaling in the mammalian cochleovestibular hair cells and afferent neurons is reviewed. The scope includes P2 and P1 receptors in the inner hair cells (IHCs) of the cochlea, the type I spiral ganglion neurons (SGNs) that convey auditory signals from IHCs, the vestibular hair cells (VHCs) in the vestibular end organs (macula in the otolith organs and crista in the semicircular canals), and the vestibular ganglion neurons (VGNs) that transmit postural and rotatory information from VHCs. Various subtypes of P2X ionotropic receptors are expressed in IHCs as well as P2Y metabotropic receptors that mobilize intracellular calcium. Their functional roles still remain speculative, but adenosine 5′-triphosphate (ATP) could regulate the spontaneous activity of the hair cells during development and the receptor potentials of mature hair cells during sound stimulation. In SGNs, P2Y metabotropic receptors activate a nonspecific cation conductance that is permeable to large cations as NMDG + and TEA + . Remarkably, this depolarizing nonspecific conductance in SGNs can also be activated by other metabotropic processes evoked by acetylcholine and tachykinin. The molecular nature and the role of this depolarizing channel are unknown, but its electrophysiological properties suggest that it could lie within the transient receptor potential channel family and could regulate the firing properties of the afferent neurons. Studies on the vestibular partition (VHC and VGN) are sparse but have also shown the expression of P2X and P2Y receptors. There is still little evidence of functional P1 (adenosine) receptors in the afferent system of the inner ear.

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“…Due to the distribution of klotho close to the Na-K-Cl co-transporter and the involvement of klotho with other proteins that regulate calcium homeostasis, e.g., transient receptor potential (TRPV), it was suggested that klotho participates in the regulation of the ionic composition of the endolymph; furthermore, the expression of klotho in the inner-ear sensory cell of the mouse led to the hypothesis that klotho is involved in signal transduction in the inner ear (Takumida et al, 2009). The expression of klotho was found to be closely related to the lifespan of the organism and klotho seems to have a protective effect against oxidative stress and to increase cell resistance to the subsequent damage (Yamamoto et al, 2005;Ikushima et al, 2006).…”

Section: Geneticsmentioning

confidence: 99%

“…Klotho is expressed predominantly in tissues involved in the regulation of calcium homeostasis and was found in the stria vascularis and the vestibular dark cells of the inner ear (Kamemori et al, 2002;Takumida et al, 2009). Due to the distribution of klotho close to the Na-K-Cl co-transporter and the involvement of klotho with other proteins that regulate calcium homeostasis, e.g., transient receptor potential (TRPV), it was suggested that klotho participates in the regulation of the ionic composition of the endolymph; furthermore, the expression of klotho in the inner-ear sensory cell of the mouse led to the hypothesis that klotho is involved in signal transduction in the inner ear (Takumida et al, 2009).…”

Section: Geneticsmentioning

confidence: 99%

Aging of the auditory system

Roth

2015

The Human Auditory System - Fundamental Organization and Clinical Disorders

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Age-dependent changes in the expression of klotho protein, TRPV5 and TRPV6 in mouse inner ear

Cited by 40 publications

References 18 publications

Calcium Oxalate Stone Formation in the Inner Ear as a Result of an Slc26a4 Mutation

Calcium Oxalate Stone Formation in the Inner Ear as a Result of an Slc26a4 Mutation

Purinergic signaling in cochleovestibular hair cells and afferent neurons

Aging of the auditory system

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