Skip to Content
MilliporeSigma
HomeCell SignalingTransient Receptor Potential Channels

Transient Receptor Potential Channels

The transient receptor potential family of ion channels consists of at least 28 mammalian members divided into six subfamilies: 7 TRPC (canonical), 6 TRPV (vanilloid), 8 TRPM (melastatin), 1 TRPA (ankyrin), 3 TRPP (polycystin) and 2 TRPML (mucolipin). Numerous invertebrate TRP channels have also been identified, including the prototypical “transient receptor potential” channels from Drosophila photoreceptors, TRP and TRP-like, and there is growing evidence for evolutionary conservation of their roles in cellular physiology and sensory biology.

Structurally, TRP channels have six transmembrane domains and intracellular amino and carboxyl termini. Four subunits apparently comprise a functional channel. Other features shared by some, but not all, TRP channels include a TRP-domain found in the proximal portion of the sixth transmembrane domain of all TRPC and some TRPM channels, and a string of 3-14 ankyrin repeat domains found in the amino terminus of TRPC, TRPV and TRPA channels. Sequence homology among all family members is concentrated in ankyrin repeat, transmembrane, and TRP domains, and can be as little as ~20% overall. Functionally, TRP channels are versatile molecules that can be gated by G protein-coupled receptor (GPCR) signaling, lipids, ions, osmolarity, voltage, or even hot and cold temperatures. Upon activation, these channels mediate the influx of monovalent and/or divalent cations into excitable and nonexcitable cells.

There appears to be only one mammalian member of the TRPA subfamily, referred to as TRPA1. This channel contains 14 ankyrin repeat domains in its amino terminus. It is expressed in several locations, including a subset of primary sensory neurons and in hair cells of the inner ear. This channel can be activated by pungent compounds such as mustard oil (allyl isothiocyanate) or cinnamaldehyde. It has also been reported to be activated by painful cold (<20 °C), although this claim has been disputed. There is also evidence that TRPA1 may contribute to mechanotransduction mechanisms in the auditory and vestibular systems.

The TRPC subfamily can be further subdivided into several groups. TRPC1 is a widely distributed subtype that can form heteromultimers with other TRPC subfamily members. The TRPC2 gene is expressed in rodents, but is a psudogene in humans. This channel is specifically expressed in the sensory cilia of vomeronasal organ pheromone sensing cells, and is essential for certain GPCR-mediated pheromone-driven behaviors in mice. TRPC4 and TRPC5 form homomultimeric channels, as well as heteromultimers that include TRPC1. They are activated by Gq-coupled GPCR signaling pathways via an as yet unidentified mechanism. TRPC3, TRPC6, and TRPC7 can be activated directly by diacylglycerol. All TRPC channels pass nonselective cationic currents. It is believed that some TRPC channels participate in so-called “store-operated” Ca2+ entry into cells following depletion of IP3 receptor-dependent intracellular Ca2+ stores. However, the mechanisms underlying this process have been debated. One proposal suggests conformational coupling between intracellular IP3 receptors and cell surface TRPC channels. Other investigators have argued for the existence of a diffusible messenger that regulates store-operated channel function.

The TRPM subfamily is characterized by exceptionally long amino and/or carboxyl terminal domains. TRPM1 is downregulated during metastatic progression of melanoma cells, although its functional properties are unknown. TRPM2 is a nonselective cation channel possessing a C-terminal NUDIX domain that allows this channel to be activated by ADP-ribose, NAD and reactive oxygen species. TRPM3 forms a nonselective cation channel with constitutive activity that can be augmented by hypoosmolarity and may play a role in renal Ca2+ homeostasis. TRPM4 and TRPM5 are voltage-dependent channels selective for monovalent cations that both exhibit extracellular Ca2+-dependent activation. Furthermore, TRPM4 can be regulated by intracellular adenine nucleotides or by decavanadate ions. TRPM6 and TRPM7 appear to form heteromultimeric divalent cation-selective channels that are critical for Mg2+ homeostasis in humans. They also contain an intrinsic kinase domain within their carboxyl terminus that regulates responsiveness to intracellular Mg2+. TRPM8, originally identified as being prostate-specific, was subsequently found to be expressed in a subset of sensory neurons and to respond to modestly cold temperatures (<28 °C) and the cold-mimetic chemicals, menthol and icilin. Icilin activation, however, requires intracellular Ca2+ as a co-agonist. This nonselective cation channel also exhibits voltage-dependent opening.

The TRPV subfamily is so-named because its founding member, TRPV1, is the receptor for capsaicin, the major pungent component of “hot” chili peppers and other compounds (e.g., resiniferatoxin) that possess a similar vanilloid chemical moiety. This channel is highly expressed in nociceptive sensory neurons that detect painful stimuli. TRPV1 can also be activated by protons, endocannabinoid compounds, or elevated temperature (>42 °C). Accordingly, responses to all of these stimuli are diminished or absent in TRPV1 knockout mice. TRPV2, TRPV3, and TRPV4 can also be activated by heat, with temperature thresholds of ~ 52 °C, ~34 °C and ~27 °C, respectively. Alternatively, TRPV4 can be activated by hypoosmolarity or certain epoxyeicosatrienoic acids and TRPV2 can be activated by hypoosmolarity or growth factor receptor stimulation. TRPV4 is necessary for normal maintenance of serum osmolarity in the mouse. All four of these proteins form homomultimeric nonselective cation channels with a PCa:PNa of 5-10:1. TRPV5 and TRPV6 form homomultimeric and heteromultimeric Ca2+-selective channels that exhibit constitutive activity and participate in Ca2+ uptake in the intestine and kidney.

The Tables below contain accepted modulators and additional information. For a list of additional products, see the "Similar Products" section below.

Ankyrin and Canonical Subfamilies

NameTRPA1TRPC1TRPC2TRPC3
Alternative NamesANKTM1TRP1Not KnownmTRPC3
Structural Information1119 aa (human)
1125 aa (mouse)
793 aa (human)
809 aa (mouse)
Human pseudogene
1172 aa (mouse)
848 aa(human)
836 aa (mouse)
ActivatorsMustard oil (W203408)
Cinnamaldehyde (W228613)
Ca2+ (intracellular)
Cold (<20°C)
THC (T2386)
GPCR-Gq -PLCGPCR-Gq -PLCDAG
Direct interaction with IP3R
InhibitorsRuthenium red (R2751)
Gd3+ (homomer)
2-APB (heteromer w/C1) (D9754)
La3+ (heteromer w/C1)
Gd3+ (homomer)
High external Ca2+
2-APB (D9754)
Not Known2-APB (D9754)
PMA (P8139)
ModulatorsIcilin (I9532)Calmodulin (P0270P1431)Not Known
Not Known
Signal Transduction
Mechanism
Non-selective cation channelNon-selective cation channelNon-selective cation channelNon-selective cation channel
Radioligand of ChoiceNot KnownNot KnownNot KnownNot Known
Tissue ExpressionSensory neurons, inner ear hair cells, vestibular organHeart, brain, testis, ovaryVomeronasal organ, testisBrain
Physiological Effects (demonstrated or speculated)Cold-evoked pain, chemically evoked painCellular Ca2+ homeostasisPheromone detectionCellular Ca2+ homeostasis
Disease States (demonstrated
or speculated)
Chronic pain, cancer, deafnessNot KnownUnlikely in humansNot Known
NameTRPC4TRPC5TRPC6TRPC7
Alternative NamesTRP4, CCE1, bCCETRP5, CCE2Not KnownTRP7
Structural Information982 aa (human)973 aa (human)
975 aa (mouse)
931aa (human)
930aa (mouse)
862aa (human)
862 aa (mouse)
ActivatorsWeakly voltage dependent
GPCR-Gq -PLC
Weakly voltage dependent
GPCR-Gq -PLC
DAGDAG
Inhibitors2-APB (D9754)2-APB (D9754)Not KnownLa3+
SKF96365 (S7809)
ModulatorsLa3+ (augments currents)La3+ (augments currents)Not KnownExtracellular ATP
intracellular Ca2+
PKC
Signal Transduction MechanismNon-selective cation channelNon-selective cation channelNon-selective cation channelNon-selective cation channel
Radioligand of ChoiceNot KnownNot KnownNot KnownNot Known
Tissue ExpressionBrain, endothelium, adrenal gland, retina, testisBrainLung, brainEye, heart, lung
Physiological Effects (demonstrated or speculated)Cellular Ca2+ homeostasis, vascular tone, permeability, neurotransmitter releaseCellular Ca2+ homeostasis, neurite outgrowthCellular Ca2+ homeostasis, cerebrovascular toneCellular Ca2+ homeostasis
Disease States (demonstrated or speculated)HypertensionNot KnownNot KnownNot Known

Abbreviations

2APB: 2-Aminoethoxydiphenyl borate
SB366791: N-(3-Methoxyphenyl)-4-chlorocinnamide
BCTC: N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide
EGF: Epidermal growth factor
GPCR: G protein-coupled receptor
4α-PDD: 4 α-Phorbol didecanoate
DAG: Diacylglycerol
IP3R: Inositol triphosphate receptor
NAD: Nicotinamide adenine dinucleotide
NUDIX: Nucleoside diphosphate pyrophosphatase
PMA: Phorbol myristoyl acetate
PIP2: Phosphatidyl inositol bisphosphate
PLC: Phospholipase C
THC: Δ 9-Tetrahydrocannabinol

Melastatin Subfamily

NameTRPM1TRPM2TRPM3TRPM4
Alternative NamesMelastatinTRPC7, LTRPC7KIAA1616, LTRPC3FLJ20041, LTRPC4
Structural Information1533 aa (human)
1749 aa (mouse)
1503 aa (human)
1507 aa (mouse)
C term. NUDIX domain
1707 aa (human)
1337 aa (mouse)
1214aa (human)
945 aa (mouse)
ActivatorsConstitutively activeβ-NAD
ADP-ribose (A0752)
H2O2 (H3410)
ConstitutiveExtracellular Ca2+
InhibitorsLa3+Na+Not Known
Mg2+
La3+
Adenine nucleotides
ModulatorsNot KnownIntracellular Ca2+
TNFα (T7539T6674T5944)
Arachidonic acid (A3555A3611A8798)
Hypotonicity (increase)Decavanadate
Signal Transduction MechanismNon-selective cation channelNon-selective cation channelNon-selective cation channelMonovalent-selective cation channel
Radioligand of ChoiceNot KnownNot KnownNot KnownNot Known
Tissue ExpressionEye, melanocytesBrain, pancreas, neutrophilsKidney, brainProstate, colon, heart, kidney, neurons
Physiological Effects (demonstrated or speculated)Tumor supressor, calcium homeostasisOxidative stress response, apoptosisRenal calcium homeostasisCellular Ca2+ homeostasis
Disease States (demonstrated or speculated)MelanomaNot KnownNot KnownNot Known
NameTRPM5TRPM6TRPM7TRPM8
Alternative NamesMtrl, LTRPC5ChaK2TRP-PLIK, LTRPC7, ChaK(1)Trp-p8, CMR1
Structural Information1165 aa (human)
1148 aa (mouse)
2022 aa (human)
2028 aa (mouse)
C term. a-kinase domain
1865 aa (human)
1863 aa (mouse)
C term. a-kinase domain
1104 aa (human)
1104 aa (mouse)
ActivatorsExtracellular Ca2+Low intracellular
Mg2+ and Mg2+ ATP
Low intracellular
Mg2+ and Mg2+ ATP
Constitutive
Menthol (M2772)
Icilin (I9532) (coagonist w/Ca2+)
Cold (<27 °C)
Eucalyptol (C80601)
InhibitorsNot Known
Not Known
Mg2+
La3+
2-APB (D9754)
Low pH
ModulatorsPIP2 (P9763)Not Known
PIP2? (P9763)Not Known
Signal Transduction MechanismMonovalent-selective cation channelCa2+- and Mg2+- selective channelCa2+- and Mg2+- selective channelNon-selective cation channel
Radioligand of ChoiceNot KnownNot KnownNot KnownNot Known
Tissue ExpressionSmall intestine, liver, lungColon, kidneyKidney, heartProstate, sensory neurons
Physiological Effects (demonstrated or speculated)Taste transductionCell Mg2+ homeostasis, Mg2+ absorbtionCell Mg2+ homeostasis, Mg2+ absorbtionCold sensation, cancer
Disease States (demonstrated or speculated)Not KnownNot Known
HypomagnesemiaCold pain, prostate cancer

Abbreviations

2APB: 2-Aminoethoxydiphenyl borate
SB366791: N-(3-Methoxyphenyl)-4-chlorocinnamide
BCTC: N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide
EGF: Epidermal growth factor
GPCR: G protein-coupled receptor
4α-PDD: 4 α-Phorbol didecanoate
DAG: Diacylglycerol
IP3R: Inositol triphosphate receptor
NAD: Nicotinamide adenine dinucleotide
NUDIX: Nucleoside diphosphate pyrophosphatase
PMA: Phorbol myristoyl acetate
PIP2: Phosphatidyl inositol bisphosphate
PLC: Phospholipase C
THC: Δ 9-Tetrahydrocannabinol

Vanilloid Subfamily

NameTRPV1TRPV2TRPV3
Alternative NamesVanilloid receptor (VR1), Capsaicin receptorVRL-1, GRC, OTRPC1VRL-3, OTRPC2
Structural Information839 aa (human)
839 aa (mouse)
764 aa (human)
756 aa (mouse)
790 aa (human)
791 aa (mouse) 
Subtype-Selective AgonistsCapsaicin (M2028)
Resiniferatoxin (R8756)
Olvanil (O0257)
Nuvanil
N-arachidonyl dopamine (A8848)    
Not Known
Not Known
Activators with other Known TargetsAnandamide (A0580)
Protons
2-APB (D9754)
Heat (>42 °C)
Hypoosmolarity
heat (>52 °C)
2-APB (D9754)
Heat (>34 °C)
2-APB (D9754)
Receptor-Selective AntagonistsSB366791 (S0441)
5'-iodoresiniferatoxin (I9281)
Not Known
Not Known
Antagonists with other Known ActivitiesCapsazepine (C191)
BCTC (SML0355)
Ruthenium red (R2751)
Ruthenium red (R2751)Ruthenium red (R2751)
ModulatorsProtons
Sulfhydryl reagents
Nerve growth factor (indirect)
GPCR-Gq activation (indirect)
EGF (indirect)Not Known
Signal Transduction MechanismNon-selective cation channelNon-selective cation channelNon-selective cation channel
Radioligand of Choice[3H] ResiniferatoxinNot Known
Not Known
Tissue ExpressionSensory neurons, brain, urinary bladder epithelium, skin keratinocytes, mast cells, hepatocytesSensory neurons, brain, lung, skeletal, cardiac muscle, intestines, mast cellsSensory neurons, brain, skin keratinocytes, testis
Physiological Effects (demonstrated or speculated)Pain sensation, bladder contraction, vasomotor regulation, immunoregulationPain sensation, Mast cell functionPain, warmth sensation
Disease States (demonstrated or speculated)Chronic pain, bladder hyperactivity, inflammatory bowel disease, Prurigo nodularisChronic painChronic pain
NameTRPV4TRPV5TRPV6
Alternative NamesVRL-2, Trp12, VR-OAC, OTRPC4ECaC1, CaT2, OTRPC3ECaC2, CaT1, CaT-like
Structural Information871 aa (human)
871 aa (mouse)
729 aa (human)
723 aa (mouse)
725 aa (human)
727 aa (mouse) 
Subtype-Selective Agonists4α-PDDNot Known
Not Known
Activators with other Known TargetsHypoosmolarity
Heat (>27 °C)
5', 6'-eicosatrienoic acid
Not Known
Not Known
Receptor-Selective AntagonistsNot Known
Not Known
Not Known
Antagonists with other Known ActivitiesRuthenium red (R2751)Ruthenium red (R2751)
2-APB (D9754)
Ruthenium red (R2751)
ModulatorsNot Known
Vitamin D (expression level)Vitamin D (expression level)
2-APB (D9754)
Signal Transduction
Mechanism
Non-selective cation channelCa2+-preferring cation channelCa2+-preferring cation channel
Radioligand of ChoiceNot Known
Not Known
Not Known
Tissue ExpressionKidney nephron, brain, skin keratinocytes, sensory neurons, respiratory epithelium, smooth muscleKidney, small intestine, placenta, pancreasSmall intestine, pancreas, placenta
Physiological Effects (demonstrated or speculated)Pain, warmth sensation, osmoregulation, mechanosensationCalcium absorptionCalcium absorption
Disease States (demonstrated
or speculated)
Chronic pain, diabetes insipidus, asthmaHypocalcemiaHypocalcemia

Abbreviations

2APB: 2-Aminoethoxydiphenyl borate
SB366791: N-(3-Methoxyphenyl)-4-chlorocinnamide
BCTC: N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide
EGF: Epidermal growth factor
GPCR: G protein-coupled receptor
4α-PDD: 4 α-Phorbol didecanoate
DAG: Diacylglycerol
IP3R: Inositol triphosphate receptor
NAD: Nicotinamide adenine dinucleotide
NUDIX: Nucleoside diphosphate pyrophosphatase
PMA: Phorbol myristoyl acetate
PIP2: Phosphatidyl inositol bisphosphate
PLC: Phospholipase C
THC: Δ 9-Tetrahydrocannabinol

Similar Products
Sorry, an unexpected error has occurred

Network error: Failed to fetch

References

1.
Abriel H, Syam N, Sottas V, Amarouch MY, Rougier J. 2012. TRPM4 channels in the cardiovascular system: Physiology, pathophysiology, and pharmacology. Biochemical Pharmacology. 84(7):873-881. https://doi.org/10.1016/j.bcp.2012.06.021
2.
Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A. 2004. Noxious Cold Ion Channel TRPA1 Is Activated by Pungent Compounds and Bradykinin. Neuron. 41(6):849-857. https://doi.org/10.1016/s0896-6273(04)00150-3
3.
Benham CD, Gunthorpe MJ, Davis JB. 2003. TRPV channels as temperature sensors. Cell Calcium. 33(5-6):479-487. https://doi.org/10.1016/s0143-4160(03)00063-0
4.
Caterina MJ, Julius D. 2001. The Vanilloid Receptor: A Molecular Gateway to the Pain Pathway. Annu. Rev. Neurosci.. 24(1):487-517. https://doi.org/10.1146/annurev.neuro.24.1.487
5.
Clapham DE, Montell C, Schultz G, Julius D. 2003. International Union of Pharmacology. XLIII. Compendium of Voltage-Gated Ion Channels: Transient Receptor Potential Channels. Pharmacol Rev. 55(4):591-596. https://doi.org/10.1124/pr.55.4.6
6.
Corey DP, García-Añoveros J, Holt JR, Kwan KY, Lin S, Vollrath MA, Amalfitano A, Cheung EL, Derfler BH, Duggan A, et al. 2004. TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature. 432(7018):723-730. https://doi.org/10.1038/nature03066
7.
Moreira F, Aguiar D, Terzian A, Guimarães F, Wotjak C. 2012. Cannabinoid type 1 receptors and transient receptor potential vanilloid type 1 channels in fear and anxiety?two sides of one coin?. Neuroscience. 204186-192. https://doi.org/10.1016/j.neuroscience.2011.08.046
8.
Fleig A, Penner R. 2004. The TRPM ion channel subfamily: molecular, biophysical and functional features. Trends in Pharmacological Sciences. 25(12):633-639. https://doi.org/10.1016/j.tips.2004.10.004
9.
Freichel M, Vennekens R, Olausson J, Hoffmann M, Müller C, Stolz S, Scheunemann J, Weißgerber P, Flockerzi V. 2004. Functional role of TRPC proteins in vivo: lessons from TRPC-deficient mouse models. Biochemical and Biophysical Research Communications. 322(4):1352-1358. https://doi.org/10.1016/j.bbrc.2004.08.041
10.
Jordt S, Bautista DM, Chuang H, McKemy DD, Zygmunt PM, Högestätt ED, Meng ID, Julius D. 2004. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature. 427(6971):260-265. https://doi.org/10.1038/nature02282
11.
Kang SS, Shin SH, Auh C, Chun J. 2012. Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation. Exp Mol Med. 44(12):707. https://doi.org/10.3858/emm.2012.44.12.080
12.
Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Bruford EA, Caterina MJ, Clapham DE, Harteneck C, Heller S, Julius D, et al. 2002. A Unified Nomenclature for the Superfamily of TRP Cation Channels. Molecular Cell. 9(2):229-231. https://doi.org/10.1016/s1097-2765(02)00448-3
13.
Montell C. 2001. Physiology, Phylogeny, and Functions of the TRP Superfamily of Cation Channels. Science Signaling. 2001(90):re1-re1. https://doi.org/10.1126/stke.2001.90.re1
14.
Moran MM, McAlexander MA, Bíró T, Szallasi A. 2011. Transient receptor potential channels as therapeutic targets. Nat Rev Drug Discov. 10(8):601-620. https://doi.org/10.1038/nrd3456
15.
Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AEH, Lu W, Brown EM, Quinn SJ, et al. 2003. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 33(2):129-137. https://doi.org/10.1038/ng1076
16.
Raychowdhury MK. Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel. Human Molecular Genetics. 13(6):617-627. https://doi.org/10.1093/hmg/ddh067
17.
Wescott SA, Rauthan M, Xu XS. 2013. When a TRP goes bad: Transient receptor potential channels in addiction. Life Sciences. 92(8-9):410-414. https://doi.org/10.1016/j.lfs.2012.07.008
Sign In To Continue

To continue reading please sign in or create an account.

Don't Have An Account?