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Results for “Transient Receptor Potential Channels”

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PubMed2003

Involvement of transient receptor potential-like channels in responses to mGluR-I activation in midbrain dopamine neurons.

We investigated the involvement of store-operated channels (SOCs) and transient receptor potential (TRP) channels in the response to activation of the group I metabotropic glutamate receptor subtype 1 (mGluR1) with the agonist (S)-3,5-dihydroxyphenylglycine (DHPG, puff application) in dopamine neurons in rat brain slices. The mGluR1-induced conductance reversed polarity close to 0 mV and at more positive potentials when extracellular potassium concentrations were increased, indicating the involvement of a cationic channel. DHPG currents but not intracellular calcium responses were reduced by low extracellular sodium concentrations but were not affected by sodium channel blockers, tetrodotoxin and saxitoxin or by inhibition of the h-current with cesium. Abolition of calcium responses with intracellular BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; 10 mm) did not affect current responses, indicating they were not calcium activated. Extracellular application of non-selective SOCs and TRP channel blockers 2-aminoethoxydiphenylborane (2-APB), SKF96365, ruthenium red and flufenamic acid (but not gadolinium) reduced DHPG current and calcium responses. Intracellular application of ruthenium red and 2-APB did not affect DHPG currents, indicating that IP3 and ryanodine receptors did not mediate their actions. Single-cell PCR revealed the presence of TRPC1 and 5 mRNA in most dopamine neurons and subtypes 3, 4 and 6 in some. Store depletion evoked calcium entry indicative of SOCs, providing the first functional observation of such channels in native central neurons. Store depletion with either cyclopiazonic acid or ryanodine abolished calcium but not current responses to DHPG. The electrophysiological and pharmacological properties of the mGluR1-induced inward current are consistent with the involvement of TRP channels whereas calcium responses are dependent on the function of SOCs in voltage clamp recordings.

Animals↗

PubMed2003

Regulation of canonical transient receptor potential (TRPC) channel function by diacylglycerol and protein kinase C.

The mechanism of receptor-induced activation of the ubiquitously expressed family of mammalian canonical transient receptor potential (TRPC) channels has been the focus of intense study. Primarily responding to phospholipase C (PLC)-coupled receptors, the channels are reported to receive modulatory input from diacylglycerol, endoplasmic reticulum inositol 1,4,5-trisphosphate receptors and Ca2+ stores. Analysis of TRPC5 channels transfected within DT40 B cells and deletion mutants thereof revealed efficient activation in response to PLC-beta or PLC-gamma activation, which was independent of inositol 1,4,5-trisphoshate receptors or the content of stores. In both HEK293 cells and DT40 cells, TRPC5 and TRPC3 channel responses to PLC activation were highly analogous, but only TRPC3 and not TRPC5 channels responded to the addition of the permeant diacylglycerol (DAG) analogue, 1-oleoyl-2-acetyl-sn-glycerol (OAG). However, OAG application or elevated endogenous DAG, resulting from either DAG lipase or DAG kinase inhibition, completely prevented TRPC5 or TRPC4 activation. This inhibitory action of DAG on TRPC5 and TRPC4 channels was clearly mediated by protein kinase C (PKC), in distinction to the stimulatory action of DAG on TRPC3, which is established to be PKC-independent. PKC activation totally blocked TRPC3 channel activation in response to OAG, and the activation was restored by PKC-blockade. PKC inhibition resulted in decreased TRPC3 channel deactivation. Store-operated Ca2+ entry in response to PLC-coupled receptor activation was substantially reduced by OAG or DAG-lipase inhibition in a PKC-dependent manner. However, store-operated Ca2+ entry in response to the pump blocker, thapsigargin, was unaffected by PKC. The results reveal that each TRPC subtype is strongly inhibited by DAG-induced PKC activation, reflecting a likely universal feedback control on TRPCs, and that DAG-mediated PKC-independent activation of TRPC channels is highly subtype-specific. The profound yet distinct control by PKC and DAG of the activation of TRPC channel subtypes is likely the basis of a spectrum of regulatory phenotypes of expressed TRPC channels.

Animals↗

PubMed2005

The role of canonical transient receptor potential 7 in B-cell receptor-activated channels.

Phospholipase C signaling stimulates Ca2+ entry across the plasma membrane through multiple mechanisms. Ca2+ store depletion stimulates store-operated Ca2+-selective channels, or alternatively, other phospholipase C-dependent events activate Ca2+-permeable non-selective cation channels. Transient receptor potential 7 (TRPC7) is a non-selective cation channel that can be activated by both mechanisms when ectopically expressed, but the regulation of native TRPC7 channels is not known. We knocked out TRPC7 in DT40 B-cells, which expresses both forms of Ca2+ entry. No difference in the store-operated current I(crac) was detected between TRPC7-/- and wild-type cells. Wild-type cells demonstrated nonstore-operated cation entry and currents in response to activation of the B-cell receptor or protease-activated receptor 2, intracellular dialysis with GTPgammaS, or application of the synthetic diacylglycerol oleyl-acetyl-glycerol. These responses were absent in TRPC7-/- cells but could be restored by transfection with human TRPC7. In conclusion, in B-lymphocytes, TRPC7 appeared to participate in the formation of ion channels that could be activated by phospholipase C-linked receptors. This represents the first demonstration of a physiological function for endogenous TRPC7 channels.

Animals↗

PubMed2006

Signaling mechanisms of down-regulation of voltage-activated Ca2+ channels by transient receptor potential vanilloid type 1 stimulation with olvanil in primary sensory neurons.

Olvanil ((N-vanillyl)-9-oleamide), a non-pungent transient receptor potential vanilloid type 1 agonist, desensitizes nociceptors and alleviates pain. But its molecular targets and signaling mechanisms are little known. Calcium influx through voltage-activated Ca(2+) channels plays an important role in neurotransmitter release and synaptic transmission. Here we determined the effect of olvanil on voltage-activated Ca(2+) channel currents and the signaling pathways in primary sensory neurons. Whole-cell voltage-clamp recordings were performed in acutely isolated rat dorsal root ganglion neurons. Olvanil (1 microM) elicited a delayed but sustained inward current, and caused a profound inhibition (approximately 60%) of N-, P/Q-, L-, and R-type voltage-activated Ca(2+) channel current. Pretreatment with a specific transient receptor potential vanilloid type 1 antagonist or intracellular application of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid abolished the inhibitory effect of olvanil on voltage-activated Ca(2+) channel current. Calmodulin antagonists (ophiobolin-A and calmodulin inhibitory peptide) largely blocked the effect of olvanil and capsaicin on voltage-activated Ca(2+) channel current. Furthermore, calcineurin (protein phosphatase 2B) inhibitors (deltamethrin and FK-506) eliminated the effect of olvanil on voltage-activated Ca(2+) channel current. Notably, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, calmodulin antagonists, and calcineurin inhibitors each alone significantly increased the amplitude of voltage-activated Ca(2+) channel current. In addition, double immunofluorescence labeling revealed that olvanil induced a rapid internalization of Ca(V)2.2 immunoreactivity from the membrane surface of dorsal root ganglion neurons. Collectively, this study suggests that stimulation of non-pungent transient receptor potential vanilloid type 1 inhibits voltage-activated Ca(2+) channels through a biochemical pathway involving intracellular Ca(2+)-calmodulin and calcineurin in nociceptive neurons. This new information is important for our understanding of the signaling mechanisms of desensitization of nociceptors by transient receptor potential vanilloid type 1 analogues and the feedback regulation of intracellular Ca(2+) and voltage-activated Ca(2+) channels in nociceptive sensory neurons.

Animals↗

PubMed2004

The canonical transient receptor potential 6 channel as a putative phosphatidylinositol 3,4,5-trisphosphate-sensitive calcium entry system.

We previously reported that phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), a lipid product of phosphoinositide 3-kinase (PI3K), induced Ca(2+) influx via a noncapacitative pathway in platelets, Jurkat T cells, and RBL-2H3 mast cells. The identity of this Ca(2+) influx system, however, remains unclear. Here, we investigate a potential link between PIP(3)-sensitive Ca(2+) entry and the canonical transient receptor potential (TRPC) channels by developing stable human embryonic kidney (HEK) 293 cell lines expressing TRPC1, TRPC3, TRPC5, and TRPC6. Two lines of evidence support TRPC6 as a putative target by which PIP(3) induces Ca(2+) influx. First, Fura-2 fluorometric Ca(2+) analysis shows the ability of PIP(3) to selectively stimulate [Ca(2+)](i) increase in TRPC6-expressing cells. Second, pull-down analysis indicates specific interactions between biotin-PIP(3) and TRPC6 protein. Our data indicate that PIP(3) activates store-independent Ca(2+) entry in TRPC6 cells via a nonselective cation channel. Although the activating effect of PIP(3) on TRPC6 is reminiscent to that of 1-oleoyl-2-acetyl-sn-glycerol, this activation is not attributable to the diacylglycerol substructure of PIP(3) since other phosphoinositides failed to trigger Ca(2+) responses. The PIP(3)-activated Ca(2+) entry is inhibited by known TRPC6 inhibitors such as Gd(3+) and SKF96365 and is independent of IP(3) production. Furthermore, we demonstrated that TRPC6 overexpression or antisense downregulation significantly alters the amplitude of PIP(3)- and anti-CD3-activated Ca(2+) responses in Jurkat T cells. Consequently, the link between TRPC6 and PIP(3)-mediated Ca(2+) entry provides a framework to account for an intimate relationship between PI3K and PLCgamma in initiating Ca(2+) response to agonist stimulation in T lymphocytes.

Biological Transport↗

PubMed2006

2-Aminoethoxydiphenyl borate inhibits KCl-induced vascular smooth muscle contraction.

K(+)-depolarization (KCl)-activated Ca(2+) entry permitting sustained force-maintenance in tonic vascular smooth muscle has long been attributed solely to activation of L-type voltage-operated Ca(2+) channels (VOCs). We used the transient receptor potential channel (TRP) blocker, 2-aminoethoxydiphenyl borate (2-APB), to test the hypothesis that KCl activates additional Ca(2+) entry pathways. 2-APB alone caused a transient weak increase in force, a sustained weak increase in basal [Ca(2+)](i) and myosin light chain phosphorylation, and inhibition of KCl-induced force, [Ca(2+)](i) and myosin light chain phosphorylation. 2-APB did not appear to block VOCs, because 2-APB did not inhibit 30 nM Bay k 8644-induced increases in [Ca(2+)](i). Moreover, although 1 microM nifedipine abolished the increase in [Ca(2+)](i) produced by alpha-adrenergic receptor activation, 2-APB produced an additional reduction in [Ca(2+)](i) below the basal level. These data support the conclusion that membrane depolarization activates 2-APB-sensitive TRPs in addition to VOCs to permit strong force-maintenance in tonic vascular smooth muscle.

Animals↗

PubMed2005

Activation of the transient receptor potential M2 channel and poly(ADP-ribose) polymerase is involved in oxidative stress-induced cardiomyocyte death.

Overproduction of reactive oxygen species is one of the major causes of cell death in ischemic-reperfusion (I/R) injury. In I/R animal models, electron microscopy (EM) has shown mixed apoptotic and necrotic characteristics in the same cardiomyocyte. The present study shows that H(2)O(2) activates both apoptotic and necrotic machineries in the same myocyte and that the ultrastructure seen using EM is very similar to that in I/R animal studies. The apoptotic component is caused by the activation of clotrimazole-sensitive, NAD(+)/ADP ribose/poly(ADP-ribose) polymerase (PARP)-dependent transient receptor potential M2 (TRPM2) channels, which induces mitochondrial [Na(+)](m) (and [Ca(2+)](m)) overload, resulting in mitochondrial membrane disruption, cytochrome c release, and caspase 3-dependent chromatin condensation/fragmentation. The necrotic component is caspase 3-independent and is caused by PARP-induced [ATP](i)/NAD(+) depletion, resulting in membrane permeabilization. Inhibition of either TRPM2 or PARP activity only partially inhibits cell death, while inhibition of both completely prevents the ultrastructural changes and myocyte death.

Animals↗

PubMed2001

Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins.

We have identified and cloned a novel gene, trp-p8, by screening a prostate-specific subtracted cDNA library. The 5694-bp cDNA has a 3312-bp open reading frame, which codes for a 1104 amino acid putative protein with seven transmembrane domains. The predicted protein revealed significant homology with the transient receptor potential (trp) family of Ca(2+) channel proteins. Northern blot analysis indicated that trp-p8 expression within normal human tissues is mostly restricted to prostate epithelial cells. In situ hybridization analysis showed that trp-p8 mRNA expression was at moderate levels in normal prostate tissue and appears to be elevated in prostate cancer. Notably, trp-p8 mRNA was also expressed in a number of nonprostatic primary tumors of breast, colon, lung, and skin origin, whereas transcripts encoding trp-p8 were hardly detected or not detected in the corresponding normal human tissues.

Amino Acid Sequence↗

PubMed2003

Transient receptor potential (TRPC) channels in human sperm: expression, cellular localization and involvement in the regulation of flagellar motility.

Capacitative Ca(2+) entry is a process whereby the activation of Ca(2+) influx through the plasma membrane is triggered by depletion of intracellular Ca(2+) stores. Some transient receptor potential (TRPC) proteins have been proposed as candidates for capacitative Ca(2+) channels. Recent evidence indicates that capacitative Ca(2+) entry participates in the sperm acrosome reaction (AR), an exocytotic process necessary for fertilization. In addition, several TRPCs have been detected heterogeneously distributed in mouse sperm, suggesting that they may participate in other functions such as motility. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, RNA messengers for TRPC1, 3, 6 and 7 were found in human spermatogenic cells. Confocal indirect immunofluorescence revealed the presence of TRPC1, 3, 4 and 6 differentially localized in the human sperm, and immunogold transmission electron microscopy indicated that TRPC epitopes are mostly associated to the surface of the cells. Because all of them were detected in the flagellum, TRPC channel antagonists were tested in sperm motility using a computer-assisted assay. Our results provide what is to our knowledge the first evidence that these channels may influence human sperm motility.

Calcium Channels↗

PubMed2005

ThermoTRP channels and cold sensing: what are they really up to?

Cooling is sensed by peripheral thermoreceptors, the main transduction mechanism of which is probably a cold- and menthol-activated ion channel, transient receptor potential (melastatin)-8 (TRPM8). Stronger cooling also activates another TRP channel, TRP (ankyrin-like)-1, (TRPA1), which has been suggested to underlie cold nociception. This review examines the roles of these two channels and other mechanisms in thermal transduction. TRPM8 is activated directly by gentle cooling and depolarises sensory neurones; its threshold temperature (normally approximately 26-31 degrees C in native neurones) is very flexible and it can adapt to long-term variations in baseline temperature to sensitively detect small temperature changes. This modulation is enabled by TRPM8's low intrinsic thermal sensitivity: it is sensitised to varying degrees by its cellular context. TRPM8 is not the only thermosensitive element in cold receptors and interacts with other ionic currents to shape cold receptor activity. Cold can also cause pain: the transduction mechanism is uncertain, possibly involving TRPM8 in some neurones, but another candidate is TRPA1 which is activated in expression systems by strong cooling. However, native neurones that appear to express TRPA1 respond very slowly to cold, and TRPA1 alone cannot account readily for cold nociceptor activity or cold pain in humans. Other, as yet unknown, mechanisms of cold nociception are likely.

Adaptation, Physiological↗

PubMed2002

Cloning and functional expression of human short TRP7, a candidate protein for store-operated Ca2+ influx.

The regulation and control of plasma membrane Ca(2+) fluxes is critical for the initiation and maintenance of a variety of signal transduction cascades. Recently, the study of transient receptor potential channels (TRPs) has suggested that these proteins have an important role to play in mediating capacitative calcium entry. In this study, we have isolated a cDNA from human brain that encodes a novel transient receptor potential channel termed human TRP7 (hTRP7). hTRP7 is a member of the short TRP channel family and is 98% homologous to mouse TRP7 (mTRP7). At the mRNA level hTRP7 was widely expressed in tissues of the central nervous system, as well as some peripheral tissues such as pituitary gland and kidney. However, in contrast to mTRP7, which is highly expressed in heart and lung, hTRP7 was undetectable in these tissues. For functional analysis, we heterologously expressed hTRP7 cDNA in an human embryonic kidney cell line. In comparison with untransfected cells depletion of intracellular calcium stores in hTRP7-expressing cells, using either carbachol or thapsigargin, produced a marked increase in the subsequent level of Ca(2+) influx. This increased Ca(2+) entry was blocked by inhibitors of capacitative calcium entry such as La(3+) and Gd(3+). Furthermore, transient transfection of an hTRP7 antisense expression construct into cells expressing hTRP7 eliminated the augmented store-operated Ca(2+) entry. Our findings suggest that hTRP7 is a store-operated calcium channel, a finding in stark contrast to the mouse orthologue, mTRP7, which is reported to enhance Ca(2+) influx independently of store depletion, and suggests that human and mouse TRP7 channels may fulfil different physiological roles.

Amino Acid Sequence↗

PubMed2007

Trafficking of TRP channels: determinants of channel function.

Transient receptor potential (TRP) channels are members of a relatively newly described family of cation channels that display a wide range of properties and mechanisms of activation. The exact physiological function and regulation of most of these channels have not yet been conclusively determined. Studies over the past decade have revealed important features of the channels that contribute to their function. These include homomeric interactions between TRP monomers, selective heteromeric interactions within members of the same subfamily, interactions of TRPs with accessory proteins and assembly into macromolecular signaling complexes, and regulation within functionally distinct cellular microdomains. Further, distinct constitutive and regulated vesicular trafficking mechanisms have a critical role not only in controlling the surface expression of TRP channels but also their activation in response to stimuli. A number of cellular components such as cytoskeletal and scaffolding proteins also contribute to TRP channel trafficking. Thus, mechanisms involved in the assembly and trafficking of TRP channels control their plasma membrane expression and critically impact their function and regulation.

Animals↗

PubMed2007

Influence of temperature on taste perception.

Daily experience tells us that temperature has a strong influence on how we taste. Despite the longstanding interest of many specialists in this aspect of taste, we are only starting to understand the molecular mechanisms underlying the temperature dependence of different taste modalities. Recent research has led to the identification of some strong thermosensitive molecules in the taste transduction pathway. The cold activation of the epithelial Na(+) channel and the heat activation of the taste variant of the vanilloid receptor (TRPV1t) may underlie the temperature dependence of salt responses. Heat activation of the transient receptor potential channel TRPM5 explains the enhancement of sweet taste perception by warm temperatures. Current development of methods to study taste cell physiology will help to determine the contribution of other temperature-sensitive events in the taste transduction pathways. Vice versa, the analysis of the thermodynamic properties of these events may assist to unveil the nature of several taste processes.

Animals↗

PubMed2026

Utero-placental calcium and magnesium ion channels: A systematic review of obstetric implications of their alterations.

Despite the established roles of calcium (Ca2+) and magnesium (Mg2+) in placental function and uterine contractility, limited information exists on how dysregulation of major ion channels contributes to poor pregnancy outcomes. We synthesized data on the consequences of Ca2+ and Mg2+ channelopathies in uterine and placental functions. Using PubMed, Wiley Online, AJOL, and Web of Science databases for article search, a systematic review of forty-nine papers published between 2000 and March 2026 was carried out and reported in accordance with the PRISMA 2020 guideline. Based on the PICO framework, eligible studies involving human, animal, and in vitro designs were chosen and subjected to narrative analysis. L-type and T-type voltage-gated Ca2+ channels, together with transient receptor potential channels, emerged as principal mediators of placental Ca2+ transport and myometrial contractility. Mechanosensitive Piezo1 channels mediate stretch-activated Ca2+ influx, while store-operated Ca2+ entry pathways involving STIM1-Orai1 sustain intracellular Ca2+ homeostasis. Potassium-Ca2+ coupling channels modulated membrane hyperpolarization and anti-labor effects, and intracellular regulators such as PMCA and RYR1 fine-tuned Ca2+ homeostasis. The Mg2+ transporters are essential for preserving Mg2+ homeostasis and regulating Ca2+-dependent excitability. Dysregulation of these ion channel systems was consistently linked to abnormal uterine contractility, preterm birth, preeclampsia, fetal growth restriction, and adverse pregnancy outcomes. Both Ca2+ and Mg2+ ion channelopathies represent both a potential therapeutic target and a mechanistic factor underlying key obstetric complications.

Female↗

PubMedDate not supplied

Hypertonicity-induced cation channels.

Whenever studied in a quantitative fashion, hypertonicity-induced cation channels (HICCs) are found to be the main mediators of regulatory volume increase. In most instances, these channels are either inhibited by amiloride (but insensitive to Gd3+ and flufenamate) or they are efficiently blocked by Gd3+ and flufenamate (but insensitive to amiloride). Of note, however, from two preparations so far a mixed type of pharmacology has also been reported. Whereas the ion selectivity of amiloride-sensitive HICCs has not been studied in much detail yet, amiloride-insensitive channels are either equally permeable to Na+, K+, Cs+ and Li+ but impermeable to N-methyl-D-glucamine (NMDG+) or they exhibit a permeability to Li+ and NMDG+ that amounts to some 50% when compared with that of Na+. Also in this respect, however, some peculiarities do exist. Concerning the actual molecular correlate, evidence was reported that HICCs may be related to the (amiloride-sensitive) epithelial Na+ channel and/or to transient receptor potential channels. Recent findings suggest that HICCs may contribute to cell proliferation, just as the K+ channels that are employed in regulatory volume decrease are mediators of the opposing process, i.e. apoptosis.

Amiloride↗

PubMed2006

Capacitative and 1-oleyl-2-acetyl-sn-glycerol-activated Ca(2+) entry distinguished using adenylyl cyclase type 8.

Although the molecular identity of capacitative Ca(2+) entry (CCE) channels remains elusive, transient receptor potential channel (TRPC) family members 3, 6, and 7, which are activated by diacylglycerol (DAG), have been put forward as possible candidates. Because human embryonic kidney (HEK) 293 cells endogenously express these TRP subunits, this cell line is suitable for investigating whether DAG-activated TRP subunits form part of the putative multimeric assemblies that mediate CCE. Adenylyl cyclase type 8 (AC8) is activated by CCE in nonexcitable cells but is not responsive to other forms of Ca(2+) entry, such as ionophore- or arachidonate-activated entry through the plasma membrane. In this study, we exploited this unique dependence of AC8 on CCE to determine whether the DAG analog, 1-oleyl-2-acetyl-sn-glycerol (OAG), activates the same subset of Ca(2+) channels as store depletion, which triggers CCE. In populations of HEK 293 cells, OAG evoked a faster and greater influx of Ca(2+) than CCE. Both pathways of Ca(2+) entry could be triggered simultaneously in the same batch of cells, with additive effects. It is striking that OAG-mediated Ca(2+) entry, unlike CCE, did not stimulate AC8 activity in populations of cells. In single cells, OAG evoked a highly heterogeneous response, whereas CCE occurred as a smooth and sustained increase in [Ca(2+)](i). Taken together, our results indicate that, in HEK 293 cells, OAG-activated Ca(2+) entry is distinct from CCE. The inability of the OAG-activated Ca(2+) entry pathway to regulate AC8 further reinforces the absolute dependence of this enzyme on CCE.

Adenylyl Cyclases↗

PubMedDate not supplied

Transient receptor potential (TRP) channels as potential drug targets in respiratory disease.

Calcium-permeable channels have traditionally been thought of as therapeutic targets in excitable cells. For instance, voltage-operated Ca2+ channels in neurones and smooth muscle cells for neurological and cardiovascular diseases although calcium-permeable channels are also functionally important in electrically non-excitable cells. In the lung, calcium channels play a pivotal role in the activation of all the cell types present, whether resident cells such as airway smooth muscle cells and macrophages or migratory cells such as neutrophils or lymphocytes.Previously, research in this area has been hindered by the lack of obvious molecular identity. More recently, the emergence of the transient receptor potential (TRP) cation family has yielded promising candidates which may underpin the different receptor-operated calcium influx pathways. The challenge now, is to ascribe function to the TRP channels expressed in each cell type as a first step in identifying which TRP channels may be potential drug targets for asthma and chronic obstructive pulmonary disease (COPD) (Fig. 1).

Asthma↗

PubMed2002

TRPV3 is a calcium-permeable temperature-sensitive cation channel.

Transient receptor potential (TRP) proteins are cation-selective channels that function in processes as diverse as sensation and vasoregulation. Mammalian TRP channels that are gated by heat and capsaicin (>43 degrees C; TRPV1 (ref. 1)), noxious heat (>52 degrees C; TRPV2 (ref. 2)), and cooling (< 22 degrees C; TRPM8 (refs 3, 4)) have been cloned; however, little is known about the molecular determinants of temperature sensing in the range between approximately 22 degrees C and 40 degrees C. Here we have identified a member of the vanilloid channel family, human TRPV3 (hTRPV3) that is expressed in skin, tongue, dorsal root ganglion, trigeminal ganglion, spinal cord and brain. Increasing temperature from 22 degrees C to 40 degrees C in mammalian cells transfected with hTRPV3 elevated intracellular calcium by activating a nonselective cationic conductance. As in published recordings from sensory neurons, the current was steeply dependent on temperature, sensitized with repeated heating, and displayed a marked hysteresis on heating and cooling. On the basis of these properties, we propose that hTRPV3 is thermosensitive in the physiological range of temperatures between TRPM8 and TRPV1.

Amino Acid Sequence↗