OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity

Strotmann, Rainer; Harteneck, Christian; Nunnenmacher, Karin; Schultz, Günter; Plant, Tim

doi:10.1038/35036318

Cited by 919 publications

(841 citation statements)

References 40 publications

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“…Electrophysiological studies also report aminoglycoside blockade of DRG neurons that may account for cases of aminoglycosideinduced analgesia of pain receptors (Raisinghani and Premkumar, 2005;Zhou and Zhao, 2002;Zhou et al, 2001). Hair cells and kidney cells also express a variety of transient receptor potential (TRP) channels which allow the uptake of large organic molecules, including aminoglycosides (Corey et al, 2004;Hellwig et al, 2004;Liedtke et al, 2000;Marcotti et al, 2005;Meyers et al, 2003;Raisinghani and Premkumar, 2005;Strotmann et al, 2000;Xu et al, 2002;Zheng et al, 2003). Thus, the uptake of GTTR into cells through aminoglycosidepermissive cation channels is likely to lead to diffuse cytoplasmic labeling.…”

Section: Other Sensory Locations and Mechanisms Of Uptakementioning

confidence: 99%

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

et al. 2006

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Aminoglycoside uptake in the inner ear remains poorly understood. We subcutaneously injected a fluorescently-conjugated aminoglycoside, gentamicin-Texas Red (GTTR), to investigate the in vivo uptake of GTTR in the inner ear of several vertebrates, and in various murine sensory cells using confocal microscopy.In bullfrogs, GTTR uptake was prominent in mature hair cells, but not in immature hair cells. Avian hair cells accrued GTTR more rapidly at the base of the basilar papilla. GTTR was associated with the hair bundle; and, in guinea pigs and mice, somatic GTTR fluorescence was initially diffuse before punctate (endosomal) fluorescence could be observed. A baso-apical gradient of intracellular GTTR uptake in guinea pig cochleae could only be detected at early time points (<3 h). In 21−28 day mice, cochlear GTTR uptake was greatly reduced compared to guinea pigs, 6-day-old mice, or mice treated with ethacrynic acid. In mice, GTTR was also rapidly taken up, and retained, in the kidney, dorsal root and trigeminal ganglia. In linguinal and vibrissal tissues rapid GTTR uptake cleared over a period of several days.The preferential uptake of GTTR by mature saccular, and proximal hair cells resembles the pattern of aminoglycoside-induced hair cell death in bullfrogs and chicks. Differences in the degree of GTTR uptake in hair cells of different species suggests variation in serum levels, clearance rates from serum, and/or the developmental and functional integrity of the blood-labyrinth barrier. GTTR uptake by hair cells in vivo suggests that GTTR has potential to elucidate aminoglycoside transport mechanisms into the inner ear, and as a bio-tracer for in vivo pharmacokinetic studies.

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Section: Other Sensory Locations and Mechanisms Of Uptakementioning

confidence: 99%

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

et al. 2006

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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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“…TRPV4, a functional orthologue of the C. elegans TRP channel Osm-9 [90,91], was first identified as an osmosensitive ion channel and is activated by decreased osmolarity [92][93][94]. However, subsequent studies suggest that TRPV4 is a polymodal receptor, as it can also be triggered at temperatures >25°C and protons [49,50].…”

Section: Mouse Models Deficient In Temperature Sensingmentioning

confidence: 99%

Temperature sensing across species

McKemy

2007

Pflugers Arch - Eur J Physiol

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The ability to detect changes in temperature is a fundamental sensory mechanism for every species and provides organisms with a detailed view of the environment. This review focuses on what is known of the neuronal and molecular substrates for thermosensation across species, focusing on the three robust model systems extensively used to study sensory signaling, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the laboratory mouse. Nematodes migrate to thermal climes that are amenable to their survival, a behavior that is regulated primarily through a single sensory neuron. Additionally, nematodes "learn" to seek out this temperate zone based upon their prior experience, a robust model of learning and memory. Drosophila larvae also prefer select thermal zones that are optimal for growth and have also developed vigorous mechanisms to avoid unfavorable conditions. In mammals, the transduction mechanisms for thermosensation have been identified primarily due to the fact that naturally occurring plant products evoke distinct psychophysical sensation of temperature change. More remarkably, the elucidation of the molecular sensors in mammals, along with those in Drosophila, has demonstrated conservation in the molecular mediators of temperature sensation across diverse species.

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OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity

Cited by 919 publications

References 40 publications

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

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

Temperature sensing across species

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