TRPV4 | Transient Receptor Potential channels | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

TRPV4

target has curated data in GtoImmuPdb

Target id: 510

Nomenclature: TRPV4

Family: Transient Receptor Potential channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Contents:

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 871 12q24.1 TRPV4 transient receptor potential cation channel subfamily V member 4 26
Mouse 6 1 871 5 F Trpv4 transient receptor potential cation channel, subfamily V, member 4 26
Rat 6 1 871 12q16 Trpv4 transient receptor potential cation channel 26
Previous and Unofficial Names
TRP12 | VRL-2 | CMT2C | osm-9-like TRP channel 4 | vanilloid receptor-related osmotically activated channel (Vroac) | HMSN2C | SMAL | SPSMA | SSQTL1 | osmosensitive transient receptor potential channel 4 | OTRPC4 | transient receptor potential cation channel
Database Links
CATH/Gene3D 1.25.40.20
ChEMBL Target CHEMBL3119 (Hs), CHEMBL6126 (Mm), CHEMBL2775 (Rn)
Ensembl Gene ENSG00000111199 (Hs), ENSMUSG00000014158 (Mm), ENSRNOG00000001195 (Rn)
Entrez Gene 59341 (Hs), 63873 (Mm), 66026 (Rn)
Human Protein Atlas ENSG00000111199 (Hs)
KEGG Gene hsa:59341 (Hs), mmu:63873 (Mm), rno:66026 (Rn)
OMIM 605427 (Hs)
Orphanet ORPHA171081 (Hs)
RefSeq Nucleotide NM_021625 (Hs), NM_022017 (Mm), NM_023970 (Rn)
RefSeq Protein NP_067638 (Hs), NP_071300 (Mm), NP_076460 (Rn)
UniProtKB Q9HBA0 (Hs), Q9EPK8 (Mm), Q9ERZ8 (Rn)
Wikipedia TRPV4 (Hs)
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of Xenopus tropicalis TRPV4.
PDB Id:  6BBJ
Resolution:  3.8Å
Species:  None
References:  11
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
TRPC1 28-29
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
pacsin 3 8
calmodulin 40
AQP5 27,36
Src family kinases 58
OS-9 (ER-associated protein) 50
β-catenin 38
AQP2 16
microtubule-associated protein 7 (MAP7) 41
PAR2 33
Functional Characteristics
γ = ~60 pS at –60 mV, ~90-100 pS at +60 mV; conducts mono- and di-valent cations with a preference for divalents (PCa/PNa =6–10); dual (inward and outward) rectification; potentiated by intracellular Ca2+ via Ca2+/ calmodulin; inhibited by elevated intracellular Ca2+ via an unknown mechanism (IC50 = 0.4 µM)
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  Ca2+ > Mg2+ > K+ > Cs+ > Rb+ > Na+ > Li+
References:  39,49,53
Ion Selectivity and Conductance Comments
Conductance is ~30-60 pS at -60 mV, and ~88-100 pS at +60 mV.
Voltage Dependence Comments
Activation of TRPV4 is not voltage dependent.
Other chemical activators (Human)
Epoxyeicosatrieonic acids and NO-mediated cysteine S-nitrosylation
Physical activators (Human)
Constitutively active, heat (> 24°C - 32°C), mechanical stimuli

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
GSK1016790A Hs Activation 8.7 pEC50 - Physiological 45
⤷ pEC50 8.7 (EC50 2.1x10-9 M) [45]
Holding voltage: Physiological
GSK1016790A Rn Activation 8.0 pEC50 - Physiological 55
⤷ pEC50 8.0 [55]
Holding voltage: Physiological
phorbol 12-myristate 13-acetate Hs Agonist 7.9 pEC50 - Physiological 57
⤷ pEC50 7.9 (EC50 1.25x10-8 M) [57]
Holding voltage: Physiological
GSK1016790A Mm Activation 7.7 pEC50 - Physiological 45
⤷ pEC50 7.7 [45]
Holding voltage: Physiological
4α-PDH Mm Activation 7.1 pEC50 - Physiological 21
⤷ pEC50 7.1 (EC50 7.94x10-8 M) [21]
Holding voltage: Physiological
5,6-epoxyeicosatrienoic acid Mm Agonist 6.9 pEC50 - -60.0 52
⤷ pEC50 6.9 [52]
Holding voltage: -60.0 mV
4α-PDD Mm Agonist 6.7 pEC50 - 0.0 51
⤷ pEC50 6.7 [51]
Holding voltage: 0.0 mV
4α-PDD Hs Agonist 6.5 pEC50 - - 57
⤷ pEC50 6.5 [57]
RN1747 Hs Activation 6.1 pEC50 - Physiological 48
⤷ pEC50 6.1 (EC50 7.7x10-7 M) [48]
Holding voltage: Physiological
bisandrographolide Mm Agonist 6.0 pEC50 - -60.0 37
⤷ pEC50 6.0 (EC50 1x10-6 M) [37]
Holding voltage: -60.0 mV
citric acid Mm Agonist 5.6 pEC50 - 0.0 42
⤷ pEC50 5.6 [42]
Holding voltage: 0.0 mV
phorbol 12-myristate 13-acetate Mm Agonist 5.5 pEC50 - 0.0 51
⤷ pEC50 5.5 [51]
Holding voltage: 0.0 mV
RN1747 Mm Activation 5.4 pEC50 - Physiological 48
⤷ pEC50 5.4 [48]
Holding voltage: Physiological
RN1747 Rn Activation 5.4 pEC50 - Physiological 48
⤷ pEC50 5.4 [48]
Holding voltage: Physiological
arachidonic acid Mm Activation 5.0 pEC50 - - 52
⤷ pEC50 5.0 [52]
View species-specific activator tables
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
ruthenium red Mm Antagonist - - 1x10-6 0.0 51
⤷ Conc range: 1x10-6 M [51]
Holding voltage: 0.0 mV
GSK2193874 Rn Inhibition 8.7 pEC50 - Physiological 44
⤷ pEC50 8.7 [44]
Holding voltage: Physiological
GSK2193874 Mm Inhibition 8.3 pEC50 - Physiological 44
⤷ pEC50 8.3 [44]
Holding voltage: Physiological
GSK2193874 Hs Inhibition 7.4 pEC50 - Physiological 44
⤷ pEC50 7.4 [44]
Holding voltage: Physiological
HC067047 Mm Inhibition 7.8 pIC50 - -40.0 15
⤷ pIC50 7.8 [15]
Holding voltage: -40.0 mV
HC067047 Hs Inhibition 7.3 pIC50 - -40.0 15
⤷ pIC50 7.3 (IC50 4.8x10-8 M) [15]
Holding voltage: -40.0 mV
HC067047 Rn Inhibition 6.9 pIC50 - -40.0 15
⤷ pIC50 6.9 [15]
Holding voltage: -40.0 mV
ruthenium red Rn Inhibition 6.7 pIC50 - - 19
⤷ pIC50 6.7 [19]
RN-9893 Mm Antagonist 6.5 pIC50 - - 54
⤷ pIC50 6.5 [54]
RN-9893 Hs Antagonist 6.2 pIC50 - - 54
⤷ pIC50 6.2 [54]
RN1734 Hs Inhibition 5.6 pIC50 - Physiological 48
⤷ pIC50 5.6 (IC50 2.3x10-6 M) [48]
Holding voltage: Physiological
RN1734 Rn Inhibition 5.5 pIC50 - Physiological 48
⤷ pIC50 5.5 [48]
Holding voltage: Physiological
RN1734 Mm Inhibition 5.2 pIC50 - Physiological 48
⤷ pIC50 5.2 [48]
Holding voltage: Physiological
Gd3+ Hs - - - - -
⤷
La3+ Hs - - - - -
⤷
View species-specific channel blocker tables
Immunopharmacology Comments
Expressed on mouse neutrophils [32].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0010759 positive regulation of macrophage chemotaxis IEA
GO:0050729 positive regulation of inflammatory response IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0010759 positive regulation of macrophage chemotaxis IEA
GO:0050729 positive regulation of inflammatory response IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 5 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0071639 positive regulation of monocyte chemotactic protein-1 production IEA
GO:0071642 positive regulation of macrophage inflammatory protein 1 alpha production IEA
GO:0071651 positive regulation of chemokine (C-C motif) ligand 5 production IEA
GO:2000340 positive regulation of chemokine (C-X-C motif) ligand 1 production IEA
GO:2000778 positive regulation of interleukin-6 secretion IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 5 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0010759 positive regulation of macrophage chemotaxis IEA
GO:0071639 positive regulation of monocyte chemotactic protein-1 production IEA
GO:0071642 positive regulation of macrophage inflammatory protein 1 alpha production IEA
GO:0071651 positive regulation of chemokine (C-C motif) ligand 5 production IEA
GO:2000340 positive regulation of chemokine (C-X-C motif) ligand 1 production IEA
Tissue Distribution
Trachea, kidney, liver, lung, spleen, skin.
Species:  Human
Technique:  Northern Blot
References:  9
Brain, trigeminal ganglia, cochlea, lung, spleen, kidney, testes, fat.
Species:  Mouse
Technique:  In situ hybridisation, Northern Blot.
References:  26
Heart, kidney, liver, testes.
Species:  Mouse
Technique:  Northern Blot
References:  39
Retina
Species:  Mouse
Technique:  Immunohistochemistry, immunoblot
References:  35
Cholangiocyte cilia (liver)
Species:  Rat
Technique:  Immunoblot, immunogold electron microscopy, immunofluorescence
References:  18
Urothelium lining the renal pelvis, urinary bladder, urethra and ureters
Species:  Rat
Technique:  Immunohistochemistry, immunoblot
References:  6,17
Functional Assays
Patch clamp (whole-cell and single-channel recordings).
Species:  Mouse
Tissue:  HEK 293 cells transfected with the TRPV4 vector.
Response measured:  Activation by osmotic changes.
References:  39
Patch clamp (whole-cell recordings).
Species:  Mouse
Tissue:  HEK 293, EA and mouse aortic endothelial cells.
Response measured:  Activation by 4α-phorbol 12,13-didecanoate and phorbol 12-myristate 13-acetate
References:  51
Intracellular Ca2+ imaging.
Species:  Mouse
Tissue:  CHO cells transfected with the TRPV4 vector.
Response measured:  Activation by osmotic changes.
References:  39
Patch clamp (whole-cell and single-channel recordings), intracellular Ca2+ imaging.
Species:  Mouse
Tissue:  HEK 293 cells transfected with the TRPV4 vector.
Response measured:  Activation by 5,6-epoxyeicosatrienoic acids.
References:  52
Patch clamp (whole-cell recordings), intracellular Ca2+ imaging, two-electrode voltage clamp.
Species:  Rat
Tissue:  Xenopus laevis oocytes injected with TRPV4 cDNA, HEK 293 cells transfected with the TRPV4 vector.
Response measured:  Activation by heat.
References:  19
Intracellular Ca2+ imaging, multi-electrode array recording
Species:  Mouse
Tissue:  Retinal ganglion cells
Response measured:  Activation by 4α-phorbol 12,13-didecanoate and GSK1016790A
References:  35
Intracellular Ca2+ imaging
Species:  Mouse
Tissue:  Mouse kidney M-1 (CDD) cells
Response measured:  Activation by 4α-phorbol 12,13-didecanoate, flow/shear stress and osmotic changes
References:  56
Patch clamp (whole-cell recordings), intracellular Ca2+ imaging
Species:  Mouse
Tissue:  Urothelial cells
Response measured:  Activation by 4α-phorbol 12,13-didecanoate (4α-PDD) and 4-α-phorbol 12, 13 dihexanoate (4α-PDH).
References:  14
Patch clamp (whole-cell recordings), intracellular Ca2+ imaging
Species:  Rat
Tissue:  Astrocytes
Response measured:  Activation by 4α-phorbol 12,13-didecanoate (4α-PDD)
References:  5
Physiological Functions
Thermosensation (moderate heat).
Species:  Rat
Tissue:  Thermosensory regions of the hypothalamus.
References:  19
Osmotic stimulus-induced nociception, detection and integration of osmotic/mechanical stimuli.
Species:  Rat
Tissue:  Sensory neurones.
References:  2
Osmosensation (human, rat and mouse).
Species:  Human
Tissue:  Dorsal root ganglia neurones, CHO cells, cholangiocyte cilia, retinal ganglion cells
References:  18,26,35
Stretch-activated Ca2+ channel
Species:  Mouse
Tissue:  Lung
References:  20
Mediates Ca2+ oscillations and contributes to the neurovascular coupling responses in astrocyte endfeet.
Species:  Mouse
Tissue:  Coronal brain slices
References:  12
Modulatory role in renal cyst development in autosomal recessive polycystic kidney disease (ARPKD)
Species:  Rat
Tissue:  Collecting duct (CD) cells
References:  60
Physiological Consequences of Altering Gene Expression
Sensorineural hearing impairment
Species:  Mouse
Tissue:  Cochlea.
Technique:  TRPV4 knockdown
References:  43
Impaired bladder function
Species:  Mouse
Tissue:  Bladder
Technique:  TRPV4 knockdown
References:  17
Thermal hyperalgesia.
Species:  Mouse
Tissue:  Sensory neurons.
Technique:  TRPV4 knockdown
References:  47
Suppressed unloading-induced trabecular bone loss, alterations in bone remodeling.
Species:  Mouse
Tissue:  Bone
Technique:  TRPV4 knockdown
References:  30-31
Reduced acetylcholine-induced vasodilation
Species:  Mouse
Tissue:  Arteries (mesenteric and carotid)
Technique:  TRPV4 knockdown
References:  13,61
Protection from diet-induced obesity and insulin resistance. Elevated thermogenesis in adipose tissues. Changes in fiber-type composition and oxidative capacity in skeletal muscle.
Species:  Mouse
Tissue:  Adipocytes, skeletal muscle
Technique:  TRPV4 knockdown
References:  23,59
Impairment of the intercellular junction-dependent barrier function in the skin
Species:  Mouse
Tissue:  Skin
Technique:  TRPV4 knockdown
References:  38
Reduced lung edema in response to high peak inflation pressure/ high temperature ventilation.
Species:  Mouse
Tissue:  Lung
Technique:  TRPV4 knockdown
References:  3,20
Suppressed inflammation-induced mechanical hyperalgesia
Species:  Mouse
Tissue:  Sensory neurons
Technique:  TRPV4 knockdown
References:  1
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0001422 abnormal drinking behavior PMID: 14581612 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0001784 abnormal fluid regulation PMID: 14581612 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0005316 abnormal response to tactile stimuli PMID: 12692122 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0002067 abnormal sensory capabilities/reflexes/nociception PMID: 12692122 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0008998 decreased blood osmolality PMID: 14581612 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0004765 decreased brainstem auditory evoked potential PMID: 15925108 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0005611 decreased circulating antidiuretic hormone level PMID: 14581612 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0003912 decreased drinking behavior PMID: 14581612 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0005498 hyporesponsive to tactile stimuli PMID: 14581612 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0006325 impaired hearing PMID: 15925108 
Trpv4tm1Rck Trpv4tm1Rck/Trpv4tm1Rck
Not Specified		 MGI:1926945  MP:0008997 increased blood osmolality PMID: 14581612 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0008531 increased chemical nociceptive threshold PMID: 12692122 
Trpv4tm1Msz Trpv4tm1Msz/Trpv4tm1Msz
involves: 129X1/SvJ * C57BL/6		 MGI:1926945  MP:0004597 increased susceptibility to noise-induced hearing loss PMID: 15925108 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Brachyolmia type 3
Synonyms: Autosomal dominant brachyolmia [Orphanet: ORPHA93304]
Brachyolmia [Disease Ontology: DOID:0050690]
Disease Ontology: DOID:0050690
OMIM: 113500
Orphanet: ORPHA93304
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R616Q Gain-of-function mutation 34
Missense Human V620I Gain-of-function mutation 34
Disease:  Digital arthropathy-brachydactyly; familial; FDAB
Synonyms: Familial digital arthropathy-brachydactyly [Orphanet: ORPHA85169]
OMIM: 606835
Orphanet: ORPHA85169
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human G270V Lower cell-surface expression of channel 24
Missense Human R271P Lower cell-surface expression of channel 24
Missense Human F273L Lower cell-surface expression of channel 24
Disease:  Hereditary motor and sensory neuropathy, type IIC, HMSN2C
Synonyms: Autosomal dominant Charcot-Marie-Tooth disease type 2C [Orphanet: ORPHA99937]
Charcot-Marie-Tooth disease type 2 [Disease Ontology: DOID:0050539]
Disease Ontology: DOID:0050539
OMIM: 606071
Orphanet: ORPHA99937
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R269H No activity/gain-of-function: Auer-Grumbach et al. reported that cells transfected with constructs carrying the R269H mutation did not respond to any stimulation. The TRPV4 mutants accumulated exclusively in the cytoplasm. 4,10,25
Missense Human R269C 4,10,25
Missense Human R315W No activity/gain-of-function: Auer-Grumbach et al. reported that cells transfected with constructs carrying the R315W mutation did not respond to any stimulation. The TRPV4 mutants accumulated exclusively in the cytoplasm. 4,10,25
Missense Human R316C No activity/gain-of-function: Auer-Grumbach et al. reported that cells transfected with constructs carrying the R316C mutation did not respond to any stimulation. The TRPV4 mutants accumulated exclusively in the cytoplasm. 4,10,25
Disease:  Hyponatremia
OMIM: 613508
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human P19S Tian et al reports a loss-of-function nonsynonymous polymorphism in the TRPV4 gene (P19S) associated with human hyponatremia. An expression construct carrying the TRPV4 mutant transfected in HEK cells showed diminished response to hypotonic stress. 46
Disease:  Metatropic dysplasia
OMIM: 156530
Orphanet: ORPHA2635
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human I331F Mutation causes channel to remain constitutively open 7
Missense Human P799L Mutation causes channel to remain constitutively open 7
Disease:  Parastremmatic dwarfism
OMIM: 168400
Orphanet: ORPHA2646
Disease:  Scapuloperoneal spinal muscular atrophy; SPSMA
OMIM: 181405
Disease:  Spinal muscular atrophy, distal, congenital nonprogressive
Synonyms: Autosomal dominant congenital benign spinal muscular atrophy [Orphanet: ORPHA1216]
OMIM: 600175
Orphanet: ORPHA1216
Disease:  Spondyloepiphyseal dysplasia, Maroteaux type
OMIM: 184095
Orphanet: ORPHA263482
Disease:  Spondylometaphyseal dysplasia, Kozlowski type; SMDK
OMIM: 184252
Orphanet: ORPHA93314
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human D333G Constitutively open channels 22
Missense Human R594H Constitutively open channels 22

References

Show »

1. Alessandri-Haber N, Dina OA, Joseph EK, Reichling D, Levine JD. (2006) A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators. J. Neurosci., 26 (14): 3864-74. [PMID:16597741]

2. Alessandri-Haber N, Yeh JJ, Boyd AE, Parada CA, Chen X, Reichling DB, Levine JD. (2003) Hypotonicity induces TRPV4-mediated nociception in rat. Neuron, 39 (3): 497-511. [PMID:12895423]

3. Alvarez DF, King JA, Weber D, Addison E, Liedtke W, Townsley MI. (2006) Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: a novel mechanism of acute lung injury. Circ. Res., 99 (9): 988-95. [PMID:17008604]

4. Auer-Grumbach M, Olschewski A, Papić L, Kremer H, McEntagart ME, Uhrig S, Fischer C, Fröhlich E, Bálint Z, Tang B et al.. (2010) Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C. Nat. Genet., 42 (2): 160-4. [PMID:20037588]

5. Benfenati V, Amiry-Moghaddam M, Caprini M, Mylonakou MN, Rapisarda C, Ottersen OP, Ferroni S. (2007) Expression and functional characterization of transient receptor potential vanilloid-related channel 4 (TRPV4) in rat cortical astrocytes. Neuroscience, 148 (4): 876-92. [PMID:17719182]

6. Birder L, Kullmann FA, Lee H, Barrick S, de Groat W, Kanai A, Caterina M. (2007) Activation of urothelial transient receptor potential vanilloid 4 by 4alpha-phorbol 12,13-didecanoate contributes to altered bladder reflexes in the rat. J. Pharmacol. Exp. Ther., 323 (1): 227-35. [PMID:17636010]

7. Camacho N, Krakow D, Johnykutty S, Katzman PJ, Pepkowitz S, Vriens J, Nilius B, Boyce BF, Cohn DH. (2010) Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia. Am. J. Med. Genet. A, 152A (5): 1169-77. [PMID:20425821]

8. Cuajungco MP, Grimm C, Oshima K, D'hoedt D, Nilius B, Mensenkamp AR, Bindels RJ, Plomann M, Heller S. (2006) PACSINs bind to the TRPV4 cation channel. PACSIN 3 modulates the subcellular localization of TRPV4. J. Biol. Chem., 281 (27): 18753-62. [PMID:16627472]

9. Delany NS, Hurle M, Facer P, Alnadaf T, Plumpton C, Kinghorn I, See CG, Costigan M, Anand P, Woolf CJ, Crowther D, Sanseau P, Tate SN. (2001) Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2. Physiol. Genomics, 4 (3): 165-74. [PMID:11160995]

10. Deng HX, Klein CJ, Yan J, Shi Y, Wu Y, Fecto F, Yau HJ, Yang Y, Zhai H, Siddique N et al.. (2010) Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4. Nat. Genet., 42 (2): 165-9. [PMID:20037587]

11. Deng Z, Paknejad N, Maksaev G, Sala-Rabanal M, Nichols CG, Hite RK, Yuan P. (2018) Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms. Nat. Struct. Mol. Biol., 25 (3): 252-260. [PMID:29483651]

12. Dunn KM, Hill-Eubanks DC, Liedtke WB, Nelson MT. (2013) TRPV4 channels stimulate Ca2+-induced Ca2+ release in astrocytic endfeet and amplify neurovascular coupling responses. Proc. Natl. Acad. Sci. U.S.A., 110 (15): 6157-62. [PMID:23530219]

13. Earley S, Pauyo T, Drapp R, Tavares MJ, Liedtke W, Brayden JE. (2009) TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure. Am. J. Physiol. Heart Circ. Physiol., 297 (3): H1096-102. [PMID:19617407]

14. Everaerts W, Vriens J, Owsianik G, Appendino G, Voets T, De Ridder D, Nilius B. (2010) Functional characterization of transient receptor potential channels in mouse urothelial cells. Am. J. Physiol. Renal Physiol., 298 (3): F692-701. [PMID:20015940]

15. Everaerts W, Zhen X, Ghosh D, Vriens J, Gevaert T, Gilbert JP, Hayward NJ, McNamara CR, Xue F, Moran MM et al.. (2010) Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis. Proc. Natl. Acad. Sci. U.S.A., 107 (44): 19084-9. [PMID:20956320]

16. Galizia L, Pizzoni A, Fernandez J, Rivarola V, Capurro C, Ford P. (2012) Functional interaction between AQP2 and TRPV4 in renal cells. J. Cell. Biochem., 113 (2): 580-9. [PMID:21938744]

17. Gevaert T, Vriens J, Segal A, Everaerts W, Roskams T, Talavera K, Owsianik G, Liedtke W, Daelemans D, Dewachter I et al.. (2007) Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J. Clin. Invest., 117 (11): 3453-62. [PMID:17948126]

18. Gradilone SA, Masyuk AI, Splinter PL, Banales JM, Huang BQ, Tietz PS, Masyuk TV, Larusso NF. (2007) Cholangiocyte cilia express TRPV4 and detect changes in luminal tonicity inducing bicarbonate secretion. Proc. Natl. Acad. Sci. U.S.A., 104 (48): 19138-43. [PMID:18024594]

19. Guler AD, Lee H, Iida T, Shimizu I, Tominaga M, Caterina M. (2002) Heat-evoked activation of the ion channel, TRPV4. J. Neurosci., 22 (15): 6408-14. [PMID:12151520]

20. Hamanaka K, Jian MY, Weber DS, Alvarez DF, Townsley MI, Al-Mehdi AB, King JA, Liedtke W, Parker JC. (2007) TRPV4 initiates the acute calcium-dependent permeability increase during ventilator-induced lung injury in isolated mouse lungs. Am. J. Physiol. Lung Cell Mol. Physiol., 293 (4): L923-32. [PMID:17660328]

21. Klausen TK, Pagani A, Minassi A, Ech-Chahad A, Prenen J, Owsianik G, Hoffmann EK, Pedersen SF, Appendino G, Nilius B. (2009) Modulation of the transient receptor potential vanilloid channel TRPV4 by 4alpha-phorbol esters: a structure-activity study. J. Med. Chem., 52 (9): 2933-9. [PMID:19361196]

22. Krakow D, Vriens J, Camacho N, Luong P, Deixler H, Funari TL, Bacino CA, Irons MB, Holm IA, Sadler L et al.. (2009) Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia. Am. J. Hum. Genet., 84 (3): 307-15. [PMID:19232556]

23. Kusudo T, Wang Z, Mizuno A, Suzuki M, Yamashita H. (2012) TRPV4 deficiency increases skeletal muscle metabolic capacity and resistance against diet-induced obesity. J. Appl. Physiol., 112 (7): 1223-32. [PMID:22207724]

24. Lamandé SR, Yuan Y, Gresshoff IL, Rowley L, Belluoccio D, Kaluarachchi K, Little CB, Botzenhart E, Zerres K, Amor DJ et al.. (2011) Mutations in TRPV4 cause an inherited arthropathy of hands and feet. Nat. Genet., 43 (11): 1142-6. [PMID:21964574]

25. Landouré G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC, Inada H, Shi Y, Taye AA, Kong L, Munns CH et al.. (2010) Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Nat. Genet., 42 (2): 170-4. [PMID:20037586]

26. Liedtke W, Choe Y, Martí-Renom MA, Bell AM, Denis CS, Sali A, Hudspeth AJ, Friedman JM, Heller S. (2000) Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell, 103 (3): 525-35. [PMID:11081638]

27. Liu X, Bandyopadhyay BC, Bandyopadhyay B, Nakamoto T, Singh B, Liedtke W, Melvin JE, Ambudkar I. (2006) A role for AQP5 in activation of TRPV4 by hypotonicity: concerted involvement of AQP5 and TRPV4 in regulation of cell volume recovery. J. Biol. Chem., 281 (22): 15485-95. [PMID:16571723]

28. Ma X, Nilius B, Wong JW, Huang Y, Yao X. (2011) Electrophysiological properties of heteromeric TRPV4-C1 channels. Biochim. Biophys. Acta, 1808 (12): 2789-97. [PMID:21871867]

29. Ma X, Qiu S, Luo J, Ma Y, Ngai CY, Shen B, Wong CO, Huang Y, Yao X. (2010) Functional role of vanilloid transient receptor potential 4-canonical transient receptor potential 1 complex in flow-induced Ca2+ influx. Arterioscler. Thromb. Vasc. Biol., 30 (4): 851-8. [PMID:20093626]

30. Masuyama R, Vriens J, Voets T, Karashima Y, Owsianik G, Vennekens R, Lieben L, Torrekens S, Moermans K, Vanden Bosch A et al.. (2008) TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts. Cell Metab., 8 (3): 257-65. [PMID:18762026]

31. Mizoguchi F, Mizuno A, Hayata T, Nakashima K, Heller S, Ushida T, Sokabe M, Miyasaka N, Suzuki M, Ezura Y, Noda M. (2008) Transient receptor potential vanilloid 4 deficiency suppresses unloading-induced bone loss. J. Cell. Physiol., 216 (1): 47-53. [PMID:18264976]

32. Parenti A, De Logu F, Geppetti P, Benemei S. (2016) What is the evidence for the role of TRP channels in inflammatory and immune cells?. Br. J. Pharmacol., 173 (6): 953-69. [PMID:26603538]

33. Poole DP, Amadesi S, Veldhuis NA, Abogadie FC, Lieu T, Darby W, Liedtke W, Lew MJ, McIntyre P, Bunnett NW. (2013) Protease-activated receptor 2 (PAR2) protein and transient receptor potential vanilloid 4 (TRPV4) protein coupling is required for sustained inflammatory signaling. J. Biol. Chem., 288 (8): 5790-802. [PMID:23288842]

34. Rock MJ, Prenen J, Funari VA, Funari TL, Merriman B, Nelson SF, Lachman RS, Wilcox WR, Reyno S, Quadrelli R et al.. (2008) Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia. Nat. Genet., 40 (8): 999-1003. [PMID:18587396]

35. Ryskamp DA, Witkovsky P, Barabas P, Huang W, Koehler C, Akimov NP, Lee SH, Chauhan S, Xing W, Rentería RC et al.. (2011) The polymodal ion channel transient receptor potential vanilloid 4 modulates calcium flux, spiking rate, and apoptosis of mouse retinal ganglion cells. J. Neurosci., 31 (19): 7089-101. [PMID:21562271]

36. Sidhaye VK, Guler AD, Schweitzer KS, D'Alessio F, Caterina MJ, King LS. (2006) Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions. Proc. Natl. Acad. Sci. U.S.A., 103 (12): 4747-52. [PMID:16537379]

37. Smith PL, Maloney KN, Pothen RG, Clardy J, Clapham DE. (2006) Bisandrographolide from Andrographis paniculata activates TRPV4 channels. J. Biol. Chem., 281 (40): 29897-904. [PMID:16899456]

38. Sokabe T, Fukumi-Tominaga T, Yonemura S, Mizuno A, Tominaga M. (2010) The TRPV4 channel contributes to intercellular junction formation in keratinocytes. J. Biol. Chem., 285 (24): 18749-58. [PMID:20413591]

39. Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD. (2000) OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat. Cell Biol., 2 (10): 695-702. [PMID:11025659]

40. Strotmann R, Schultz G, Plant TD. (2003) Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site. J. Biol. Chem., 278 (29): 26541-9. [PMID:12724311]

41. Suzuki M, Hirao A, Mizuno A. (2003) Microtubule-associated [corrected] protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4). J. Biol. Chem., 278 (51): 51448-53. [PMID:14517216]

42. Suzuki M, Mizuno A, Kodaira K, Imai M. (2003) Impaired pressure sensation in mice lacking TRPV4. J. Biol. Chem., 278 (25): 22664-8. [PMID:12692122]

43. Tabuchi K, Suzuki M, Mizuno A, Hara A. (2005) Hearing impairment in TRPV4 knockout mice. Neurosci. Lett., 382 (3): 304-8. [PMID:15925108]

44. Thorneloe KS, Cheung M, Bao W, Alsaid H, Lenhard S, Jian MY, Costell M, Maniscalco-Hauk K, Krawiec JA, Olzinski A et al.. (2012) An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med, 4 (159): 159ra148. [PMID:23136043]

45. Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK, McCafferty GP, Chendrimada TP, Lashinger ES, Gordon E, Evans L et al.. (2008) N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J. Pharmacol. Exp. Ther., 326 (2): 432-42. [PMID:18499743]

46. Tian W, Fu Y, Garcia-Elias A, Fernández-Fernández JM, Vicente R, Kramer PL, Klein RF, Hitzemann R, Orwoll ES, Wilmot B et al.. (2009) A loss-of-function nonsynonymous polymorphism in the osmoregulatory TRPV4 gene is associated with human hyponatremia. Proc. Natl. Acad. Sci. U.S.A., 106 (33): 14034-9. [PMID:19666518]

47. Todaka H, Taniguchi J, Satoh J, Mizuno A, Suzuki M. (2004) Warm temperature-sensitive transient receptor potential vanilloid 4 (TRPV4) plays an essential role in thermal hyperalgesia. J. Biol. Chem., 279 (34): 35133-8. [PMID:15187078]

48. Vincent F, Acevedo A, Nguyen MT, Dourado M, DeFalco J, Gustafson A, Spiro P, Emerling DE, Kelly MG, Duncton MA. (2009) Identification and characterization of novel TRPV4 modulators. Biochem. Biophys. Res. Commun., 389 (3): 490-4. [PMID:19737537]

49. Voets T, Prenen J, Vriens J, Watanabe H, Janssens A, Wissenbach U, Bödding M, Droogmans G, Nilius B. (2002) Molecular determinants of permeation through the cation channel TRPV4. J. Biol. Chem., 277 (37): 33704-10. [PMID:12093812]

50. Wang Y, Fu X, Gaiser S, Köttgen M, Kramer-Zucker A, Walz G, Wegierski T. (2007) OS-9 regulates the transit and polyubiquitination of TRPV4 in the endoplasmic reticulum. J. Biol. Chem., 282 (50): 36561-70. [PMID:17932042]

51. Watanabe H, Davis JB, Smart D, Jerman JC, Smith GD, Hayes P, Vriens J, Cairns W, Wissenbach U, Prenen J, Flockerzi V, Droogmans G, Benham CD, Nilius B. (2002) Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J. Biol. Chem., 277 (16): 13569-77. [PMID:11827975]

52. Watanabe H, Vriens J, Prenen J, Droogmans G, Voets T, Nilius B. (2003) Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature, 424 (6947): 434-8. [PMID:12879072]

53. Watanabe H, Vriens J, Suh SH, Benham CD, Droogmans G, Nilius B. (2002) Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J. Biol. Chem., 277 (49): 47044-51. [PMID:12354759]

54. Wei ZL, Nguyen MT, O'Mahony DJ, Acevedo A, Zipfel S, Zhang Q, Liu L, Dourado M, Chi C, Yip V et al.. (2015) Identification of orally-bioavailable antagonists of the TRPV4 ion-channel. Bioorg. Med. Chem. Lett., 25 (18): 4011-5. [PMID:26235950]

55. Willette RN, Bao W, Nerurkar S, Yue TL, Doe CP, Stankus G, Turner GH, Ju H, Thomas H, Fishman CE et al.. (2008) Systemic activation of the transient receptor potential vanilloid subtype 4 channel causes endothelial failure and circulatory collapse: Part 2. J. Pharmacol. Exp. Ther., 326 (2): 443-52. [PMID:18499744]

56. Wu L, Gao X, Brown RC, Heller S, O'Neil RG. (2007) Dual role of the TRPV4 channel as a sensor of flow and osmolality in renal epithelial cells. Am. J. Physiol. Renal Physiol., 293 (5): F1699-713. [PMID:17699550]

57. Xu F, Satoh E, Iijima T. (2003) Protein kinase C-mediated Ca2+ entry in HEK 293 cells transiently expressing human TRPV4. Br. J. Pharmacol., 140 (2): 413-21. [PMID:12970074]

58. Xu H, Zhao H, Tian W, Yoshida K, Roullet JB, Cohen DM. (2003) Regulation of a transient receptor potential (TRP) channel by tyrosine phosphorylation. SRC family kinase-dependent tyrosine phosphorylation of TRPV4 on TYR-253 mediates its response to hypotonic stress. J. Biol. Chem., 278 (13): 11520-7. [PMID:12538589]

59. Ye L, Kleiner S, Wu J, Sah R, Gupta RK, Banks AS, Cohen P, Khandekar MJ, Boström P, Mepani RJ et al.. (2012) TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis. Cell, 151 (1): 96-110. [PMID:23021218]

60. Zaika O, Mamenko M, Berrout J, Boukelmoune N, O'Neil RG, Pochynyuk O. (2013) TRPV4 dysfunction promotes renal cystogenesis in autosomal recessive polycystic kidney disease. J. Am. Soc. Nephrol., 24 (4): 604-16. [PMID:23411787]

61. Zhang DX, Mendoza SA, Bubolz AH, Mizuno A, Ge ZD, Li R, Warltier DC, Suzuki M, Gutterman DD. (2009) Transient receptor potential vanilloid type 4-deficient mice exhibit impaired endothelium-dependent relaxation induced by acetylcholine in vitro and in vivo. Hypertension, 53 (3): 532-8. [PMID:19188524]

Contributors

Show »

How to cite this page

Ingrid Carvacho, David E. Clapham.
Transient Receptor Potential channels: TRPV4. Last modified on 06/03/2019. Accessed on 19/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=510.