Vanilloid Receptor–Related Osmotically Activated Channel (VR-OAC), a Candidate Vertebrate Osmoreceptor

Liedtke, Wolfgang; Choe, Yong Kyung; Martí‐Renom, Marc A.; Bell, Andrea M.; Denis, Charlotte S.; AndrejŠali,; Hudspeth, A. J.; Friedman, Jeffrey M.; Heller, Stefan

doi:10.1016/s0092-8674(00)00143-4

Cited by 1,257 publications

(1,176 citation statements)

References 42 publications

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“…TRPV4 is activated by osmolarity changes [10,11], by the epoxygenase products of arachidonic acid [12], and by bisandrographolide from the medicinal plant, Andrographis Paniculata [13]. TRPV3 is activated by a number of plant extracts, such as camphor [8], carvacrol (from oregano) eugenol (from clove), and thymol (from thyme) [14].…”

Section: Introductionmentioning

confidence: 99%

The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active

Xiao¹,

Tian²,

Tang³

et al. 2008

Cell Calcium

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SummaryTRPV3 is a non-selective cation channel activated by warm to hot temperatures. In rodents, TRPV3 is highly expressed in basal keratinocytes of skin and oral/nasal epithelia. TRPV3 knockout mice showed impaired responses to innocuous and noxious heat but otherwise normal appearance and reactions to many sensory modalities. However, point mutations of TRPV3 at Gly573 to Ser and Cys have recently been linked to autosomal dominant hairless phenotypes and spontaneous dermatitis in mice and rats, implicating an important role for TRPV3 in alopecia and skin diseases. Exactly how the mutations affect TRPV3 function was unexplained. Here we show that both G573S and G573C mutations of murine TRPV3 are constitutively active in heterologous systems. In HEK293 cells, expression of the TRPV3 mutants causes cell death. In Xenopus oocytes, the constitutively active mutant channel is irresponsive to thermal and chemical stimuli but it reduces the temperature threshold and enhances the responses to heat and TRPV3 agonists of the wild type channel when they are co-expressed. We conclude that the G573S and G573C substitutions render the TRPV3 channel spontaneously active under normal physiological conditions, which in turn alters ion homeostasis and membrane potentials of skin keratinocytes, leading to hair loss and dermatitis-like skin diseases.

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Section: Introductionmentioning

confidence: 99%

The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active

Xiao¹,

Tian²,

Tang³

et al. 2008

Cell Calcium

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show abstract

“…TRPV4 has also been shown to be expressed in vertebrate cochlear hair cells and in stria vascularis (Liedtke et al 2000). Our RNA expression screen revealed a spatiodevelopmental pattern such that an increase in expression occurred in the basal quarter from E17 to P0, up to P2 in the mid-basal quarter, and P4-P6 in the apical half.…”

Section: Trp Subunits With No or Little Expression And/or No Distinctmentioning

confidence: 79%

“…Members of the TRPV channel family have been shown to play a role in sensory transduction as well as in other non-sensory pathways. TRPV4 in particular has been shown to be expressed in inner and outer hair cells, vestibular hair cells, stria vascularis, and vestibular dark cells (Liedtke et al 2000;Takumida et al 2005). Our RNA expression screen revealed spatial and/or temporal gradients in expression for most of the TRPV channels (Fig.…”

Section: Trpv Familymentioning

confidence: 82%

“…The transduction channel is a nonselective cation channel with a conductance of about 100 pS, permeable to calcium and sensitive to inhibition by TRP channel antagonists, ruthenium red, and lanthanum in turtle (Farris et al 2004) and mouse (Géléoc and Holt, unpublished). Several TRP channel subunits have been presented as hair cell transduction channel candidates, including TRPN1 (Walker et al 2000), TRPV4 (Liedtke et al 2000), TRPA1 (Corey et al 2004), and recently, TRPML3 ; Nagata et van Aken et al 2008). Yet, targeted gene deletion of single TRP genes has not revealed deficits in hair cell mechanotransduction.…”

Section: Introductionmentioning

confidence: 99%

“…Analysis of two TRP genes, TRPV4 and TRPML3, expressed in the ear revealed important nonsensory roles for TRPs in hearing and balance. TRPV4 is expressed in hair cells, stria vascularis, and vestibular dark cells (Liedtke et al 2000;Takumida et al 2005), and disruption of TRPV4 causes delayed-onset hearing loss and increases susceptibility to acoustic injury (Tabuchi et al 2005). TRPML3 is expressed in sensory hair cells and in the marginal cells of the stria vascularis (Di Palma et al 2002;Nagata et al 2008;Van Aken et al 2008).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Quantitative Analysis of the Spatiotemporal Pattern of Transient Receptor Potential Gene Expression in the Developing Mouse Cochlea

Asai

Holt

Géléoc

2009

JARO

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TRP genes encode a diverse family of ion channels which have been implicated in many sensory functions. Because several TRP channels have similar properties to the elusive hair cell transduction channel, recent attention has focused on TRP gene expression in the inner ear. At least four TRP genes are known to be expressed in hair cells: TRPC3, TRPV4, TRPA1, and TRPML3. However, there is little evidence supporting any of these as a component of the transduction complex. Other less well-characterized TRP channels are expressed in the inner ear, in particular, within the organ of Corti. Because of their potential role in sensory function, we investigated the developmental expression of RNA that encodes all 33 TRP subunits as well as several splice variants. We designed a quantitative PCR screen using cochlear samples acquired before, during, and after the time when mechanotransduction is acquired in sensory hair cells (embryonic day 17 to postnatal day 8). Cochleas, which included the organ of Corti, stria vascularis, and Reissner's membrane, were subdivided into four equal quadrants which allowed for regional comparison during development. Expression of RNA transcripts that encoded 33 TRP subunits plus several splice forms and beta-actin were quantified in 28 samples for a total of 1,092 individual measurements, each done in triplicate. We detected RNA that encoded all TRP channels except two: TRPC7 and TRPM8. The largest changes in RNA expression were for TRPA1 (9100-fold), which suggested that these subunits may contribute to normal cochlear function. Furthermore, the screen revealed TRPP3 and PKD1L3 RNA expression patterns that were correlated with the acquisition of sensory transduction in outer hair cells (Lelli et al., J Neurophysiol. 101:2961-2973, 2009). Numerous spatiotemporal expression gradients were identified many of which may contribute to the normal functional development of the mouse cochlea.

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Pain Transduction: Gating and Modulation of Ion Channels

McNaughton

2006

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Vanilloid Receptor–Related Osmotically Activated Channel (VR-OAC), a Candidate Vertebrate Osmoreceptor

Cited by 1,257 publications

References 42 publications

The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active

The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active

A Quantitative Analysis of the Spatiotemporal Pattern of Transient Receptor Potential Gene Expression in the Developing Mouse Cochlea

Pain Transduction: Gating and Modulation of Ion Channels

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