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Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor.

ABSTRACT: The detection of osmotic stimuli is essential for all organisms, yet few osmoreceptive proteins are known, none of them in vertebrates. By employing a candidate-gene approach based on genes encoding members of the TRP superfamily of ion channels, we cloned cDNAs encoding the vanilloid receptor-related osmotically activated channel (VR-OAC) from the rat, mouse, human, and chicken. This novel cation-selective channel is gated by exposure to hypotonicity within the physiological range. In the central nervous system, the channel is expressed in neurons of the circumventricular organs, neurosensory cells responsive to systemic osmotic pressure. The channel also occurs in other neurosensory cells, including inner-ear hair cells, sensory neurons, and Merkel cells.

SUBMITTER: Liedtke W

PROVIDER: S-EPMC2211528 | biostudies-literature | 2000 Oct

REPOSITORIES: biostudies-literature

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Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor.

Liedtke W W Choe Y Y Martí-Renom M A MA Bell A M AM Denis C S CS Sali A A Hudspeth A J AJ Friedman J M JM Heller S S

Cell 20001001 3

The detection of osmotic stimuli is essential for all organisms, yet few osmoreceptive proteins are known, none of them in vertebrates. By employing a candidate-gene approach based on genes encoding members of the TRP superfamily of ion channels, we cloned cDNAs encoding the vanilloid receptor-related osmotically activated channel (VR-OAC) from the rat, mouse, human, and chicken. This novel cation-selective channel is gated by exposure to hypotonicity within the physiological range. In the centr ...[more]

PMID: 11081638

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Chondroprotective role of the osmotically sensitive ion channel transient receptor potential vanilloid 4: age- and sex-dependent progression of osteoarthritis in Trpv4-deficient mice.

Project description:ObjectiveMechanical loading significantly influences the physiology and pathology of articular cartilage, although the mechanisms of mechanical signal transduction are not fully understood. Transient receptor potential vanilloid 4 (TRPV4) is a Ca(++)-permeable ion channel that is highly expressed by articular chondrocytes and can be gated by osmotic and mechanical stimuli. The goal of this study was to determine the role of Trpv4 in the structure of the mouse knee joint and to determine whether Trpv4(-/-) mice exhibit altered Ca(++) signaling in response to osmotic challenge.MethodsKnee joints of Trpv4(-/-) mice were examined histologically and by microfocal computed tomography for osteoarthritic changes and bone structure at ages 4, 6, 9, and 12 months. Fluorescence imaging was used to quantify chondrocytic Ca(++) signaling within intact femoral cartilage in response to osmotic stimuli.ResultsDeletion of Trpv4 resulted in severe osteoarthritic changes, including cartilage fibrillation, eburnation, and loss of proteoglycans, that were dependent on age and male sex. Subchondral bone volume and calcified meniscal volume were greatly increased, again in male mice. Chondrocytes from Trpv4(+/+) mice demonstrated significant Ca(++) responses to hypo-osmotic stress but not to hyperosmotic stress. The response to hypo-osmotic stress or to the TRPV4 agonist 4α-phorbol 12,13-didecanoate was eliminated in Trpv4(-/-) mice.ConclusionDeletion of Trpv4 leads to a lack of osmotically induced Ca(++) signaling in articular chondrocytes, accompanied by progressive, sex-dependent increases in bone density and osteoarthritic joint degeneration. These findings suggest a critical role for TRPV4-mediated Ca(++) signaling in the maintenance of joint health and normal skeletal structure.

| S-EPMC3027356 | biostudies-literature

Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation.

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Pharmacologic inhibition of transient receptor channel vanilloid 4 attenuates abdominal aortic aneurysm formation.

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The human transient receptor potential vanilloid 3 channel is sensitized via the ERK pathway.

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Project description:Transient receptor potential (TRP) ion channels are emerging as a new set of membrane proteins involved in a vast array of cellular processes and regulated by a large number of physical and chemical stimuli, which involves them with sensory cell physiology. The vanilloid TRP subfamily (TRPV) named after the vanilloid receptor 1 (TRPV1) consists of six members, and at least four of them (TRPV1-TRPV4) have been related to thermal sensation. One of the least characterized members of the TRP subfamily is TRPV2. Although initially characterized as a noxious heat sensor, TRPV2 now seems to have little to do with temperature sensing but a much more complex physiological profile. Here we review the available information and research progress on the structure, physiology and pharmacology of TRPV2 in an attempt to shed some light on the physiological and pharmacological deorphanization of TRPV2.

| S-EPMC3783526 | biostudies-literature

The conformational wave in capsaicin activation of transient receptor potential vanilloid 1 ion channel.

Project description:The capsaicin receptor TRPV1 has been intensively studied by cryo-electron microscopy and functional tests. However, though the apo and capsaicin-bound structural models are available, the dynamic process of capsaicin activation remains intangible, largely due to the lack of a capsaicin-induced open structural model and the low occupancy of the transition states. Here we report that reducing temperature toward the freezing point substantially increased channel closure events even in the presence of saturating capsaicin. We further used a combination of fluorescent unnatural amino acid (fUAA) incorporation, computational modeling, and rate-equilibrium linear free-energy relationships analysis (Φ-analysis) to derive the fully open capsaicin-bound state model, and reveal how the channel transits from the apo to the open state. We observed that capsaicin initiates a conformational wave that propagates through the S4-S5 linker towards the S6 bundle and finally reaching the selectivity filter. Our study provides a temporal mechanism for capsaicin activation of TRPV1.

| S-EPMC6056546 | biostudies-literature

Transient receptor potential vanilloid 4 channel deletion regulates pathological but not developmental retinal angiogenesis.

Project description:Transient receptor potential vanilloid 4 (TRPV4) channels are mechanosensitive ion channels that regulate systemic endothelial cell (EC) functions such as vasodilation, permeability, and angiogenesis. TRPV4 is expressed in retinal ganglion cells, Müller glia, pigment epithelium, microvascular ECs, and modulates cell volume regulation, calcium homeostasis, and survival. TRPV4-mediated physiological or pathological retinal angiogenesis remains poorly understood. Here, we demonstrate that TRPV4 is expressed, functional, and mechanosensitive in retinal ECs. The genetic deletion of TRPV4 did not affect postnatal developmental angiogenesis but increased pathological neovascularization in response to oxygen-induced retinopathy (OIR). Retinal vessels from TRPV4 knockout mice subjected to OIR exhibited neovascular tufts that projected into the vitreous humor and displayed reduced pericyte coverage compared with wild-type mice. These results suggest that TRPV4 is a regulator of retinal angiogenesis, its deletion augments pathological retinal angiogenesis, and that TRPV4 could be a novel target for the development of therapies against neovascular ocular diseases.

| S-EPMC7920906 | biostudies-literature

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