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TRPV4

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 510

Nomenclature: TRPV4

Family: Transient Receptor Potential channels

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 871 12q24.11 TRPV4 transient receptor potential cation channel subfamily V member 4 28
Mouse 6 1 871 5 F Trpv4 transient receptor potential cation channel, subfamily V, member 4 28
Rat 6 1 871 12q16 Trpv4 transient receptor potential cation channel, subfamily V, member 4 28
Previous and Unofficial Names Click here for help
TRP12 | VRL-2 | CMT2C | SPSMA | osm-9-like TRP channel 4 | vanilloid receptor-related osmotically activated channel (Vroac) | HMSN2C | SMAL | SSQTL1 | osmosensitive transient receptor potential channel 4 | OTRPC4 | transient receptor potential cation channel
Database Links Click here for help
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)
Pharos Q9HBA0 (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 Click here for help
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 Click here for help
Heteromeric Pore-forming Subunits
Name References
TRPC1 30-31
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
pacsin 3 8
calmodulin 42
AQP5 29,38
Src family kinases 60
OS-9 (ER-associated protein) 52
β-catenin 40
AQP2 17
microtubule-associated protein 7 (MAP7) 43
PAR2 35
Functional Characteristics Click here for help
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 Click here for help
Species:  Mouse
Rank order:  Ca2+ > Mg2+ > K+ > Cs+ > Rb+ > Na+ > Li+
References:  41,51,55
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 go icon to follow link

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 Small molecule or natural product Hs Activation 8.7 pEC50 - Physiological 47
⤷ pEC50 8.7 (EC50 2.1x10-9 M) [47]
Holding voltage: Physiological
GSK1016790A Small molecule or natural product Rn Activation 8.0 pEC50 - Physiological 57
⤷ pEC50 8.0 [57]
Holding voltage: Physiological
phorbol 12-myristate 13-acetate Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.9 pEC50 - Physiological 59
⤷ pEC50 7.9 (EC50 1.25x10-8 M) [59]
Holding voltage: Physiological
GSK1016790A Small molecule or natural product Mm Activation 7.7 pEC50 - Physiological 47
⤷ pEC50 7.7 [47]
Holding voltage: Physiological
4α-PDH Small molecule or natural product Mm Activation 7.1 pEC50 - Physiological 23
⤷ pEC50 7.1 (EC50 7.94x10-8 M) [23]
Holding voltage: Physiological
5,6-epoxyeicosatrienoic acid Small molecule or natural product Ligand is endogenous in the given species Mm Agonist 6.9 pEC50 - -60.0 54
⤷ pEC50 6.9 [54]
Holding voltage: -60.0 mV
4α-PDD Small molecule or natural product Mm Agonist 6.7 pEC50 - 0.0 53
⤷ pEC50 6.7 [53]
Holding voltage: 0.0 mV
4α-PDD Small molecule or natural product Hs Agonist 6.5 pEC50 - - 59
⤷ pEC50 6.5 [59]
RN1747 Small molecule or natural product Hs Activation 6.1 pEC50 - Physiological 50
⤷ pEC50 6.1 (EC50 7.7x10-7 M) [50]
Holding voltage: Physiological
bisandrographolide Small molecule or natural product Mm Agonist 6.0 pEC50 - -60.0 39
⤷ pEC50 6.0 (EC50 1x10-6 M) [39]
Holding voltage: -60.0 mV
citric acid Small molecule or natural product Ligand has a PDB structure Mm Agonist 5.6 pEC50 - 0.0 44
⤷ pEC50 5.6 [44]
Holding voltage: 0.0 mV
phorbol 12-myristate 13-acetate Small molecule or natural product Mm Agonist 5.5 pEC50 - 0.0 53
⤷ pEC50 5.5 [53]
Holding voltage: 0.0 mV
RN1747 Small molecule or natural product Mm Activation 5.4 pEC50 - Physiological 50
⤷ pEC50 5.4 [50]
Holding voltage: Physiological
RN1747 Small molecule or natural product Rn Activation 5.4 pEC50 - Physiological 50
⤷ pEC50 5.4 [50]
Holding voltage: Physiological
arachidonic acid Small molecule or natural product Ligand has a PDB structure Mm Activation 5.0 pEC50 - - 54
⤷ pEC50 5.0 [54]
View species-specific activator tables
Inhibitors
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
Crotamiton Small molecule or natural product Approved drug N/A Inhibition - - - - 22
⤷ [22]
Description: Whole-cell patch-clamp recordings, crotamiton strongly inhibited TRPV (vanilloid) 4 channels followed by large currents after crotamiton washout.
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 Click here for species-specific activity table Mm Antagonist - - 1x10-6 0.0 53
⤷ Conc range: 1x10-6 M [53]
Holding voltage: 0.0 mV
GSK2193874 Small molecule or natural product Rn Inhibition 8.7 pEC50 - Physiological 46
⤷ pEC50 8.7 [46]
Holding voltage: Physiological
GSK2193874 Small molecule or natural product Mm Inhibition 8.3 pEC50 - Physiological 46
⤷ pEC50 8.3 [46]
Holding voltage: Physiological
GSK2193874 Small molecule or natural product Hs Inhibition 7.4 pEC50 - Physiological 46
⤷ pEC50 7.4 [46]
Holding voltage: Physiological
HC067047 Small molecule or natural product Mm Inhibition 7.8 pIC50 - -40.0 16
⤷ pIC50 7.8 [16]
Holding voltage: -40.0 mV
HC067047 Small molecule or natural product Hs Inhibition 7.3 pIC50 - -40.0 16
⤷ pIC50 7.3 (IC50 4.8x10-8 M) [16]
Holding voltage: -40.0 mV
HC067047 Small molecule or natural product Rn Inhibition 6.9 pIC50 - -40.0 16
⤷ pIC50 6.9 [16]
Holding voltage: -40.0 mV
ruthenium red Click here for species-specific activity table Rn Inhibition 6.7 pIC50 - - 20
⤷ pIC50 6.7 [20]
RN-9893 Small molecule or natural product Mm Antagonist 6.5 pIC50 - - 56
⤷ pIC50 6.5 [56]
RN-9893 Small molecule or natural product Hs Antagonist 6.2 pIC50 - - 56
⤷ pIC50 6.2 [56]
RN1734 Small molecule or natural product Hs Inhibition 5.6 pIC50 - Physiological 50
⤷ pIC50 5.6 (IC50 2.3x10-6 M) [50]
Holding voltage: Physiological
RN1734 Small molecule or natural product Rn Inhibition 5.5 pIC50 - Physiological 50
⤷ pIC50 5.5 [50]
Holding voltage: Physiological
RN1734 Small molecule or natural product Mm Inhibition 5.2 pIC50 - Physiological 50
⤷ pIC50 5.2 [50]
Holding voltage: Physiological
Gd3+ Click here for species-specific activity table Hs - - - - -
⤷
La3+ Click here for species-specific activity table Hs - - - - -
⤷
View species-specific channel blocker tables
Immunopharmacology Comments
Expressed on mouse neutrophils [34].
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 4 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
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 Click here for help
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:  28
Heart, kidney, liver, testes.
Species:  Mouse
Technique:  Northern Blot
References:  41
Retina
Species:  Mouse
Technique:  Immunohistochemistry, immunoblot
References:  37
Urothelium lining the renal pelvis, urinary bladder, urethra and ureters
Species:  Rat
Technique:  Immunohistochemistry, immunoblot
References:  6,18
Cholangiocyte cilia (liver)
Species:  Rat
Technique:  Immunoblot, immunogold electron microscopy, immunofluorescence
References:  19
Functional Assays Click here for help
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:  41
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:  53
Intracellular Ca2+ imaging.
Species:  Mouse
Tissue:  CHO cells transfected with the TRPV4 vector.
Response measured:  Activation by osmotic changes.
References:  41
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:  54
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:  20
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:  37
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:  58
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:  15
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 Click here for help
Thermosensation (moderate heat).
Species:  Rat
Tissue:  Thermosensory regions of the hypothalamus.
References:  20
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:  19,28,37
Stretch-activated Ca2+ channel
Species:  Mouse
Tissue:  Lung
References:  21
Mediates Ca2+ oscillations and contributes to the neurovascular coupling responses in astrocyte endfeet.
Species:  Mouse
Tissue:  Coronal brain slices
References:  13
Modulatory role in renal cyst development in autosomal recessive polycystic kidney disease (ARPKD)
Species:  Rat
Tissue:  Collecting duct (CD) cells
References:  62
Physiological Consequences of Altering Gene Expression Click here for help
Sensorineural hearing impairment
Species:  Mouse
Tissue:  Cochlea.
Technique:  TRPV4 knockdown
References:  45
Thermal hyperalgesia.
Species:  Mouse
Tissue:  Sensory neurons.
Technique:  TRPV4 knockdown
References:  49
Suppressed unloading-induced trabecular bone loss, alterations in bone remodeling.
Species:  Mouse
Tissue:  Bone
Technique:  TRPV4 knockdown
References:  32-33
Reduced acetylcholine-induced vasodilation
Species:  Mouse
Tissue:  Arteries (mesenteric and carotid)
Technique:  TRPV4 knockdown
References:  14,63
Impaired bladder function
Species:  Mouse
Tissue:  Bladder
Technique:  TRPV4 knockdown
References:  18
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:  25,61
Impairment of the intercellular junction-dependent barrier function in the skin
Species:  Mouse
Tissue:  Skin
Technique:  TRPV4 knockdown
References:  40
Reduced lung edema in response to high peak inflation pressure/ high temperature ventilation.
Species:  Mouse
Tissue:  Lung
Technique:  TRPV4 knockdown
References:  3,21
Suppressed inflammation-induced mechanical hyperalgesia
Species:  Mouse
Tissue:  Sensory neurons
Technique:  TRPV4 knockdown
References:  1
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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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 Click here for help
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 36
Missense Human V620I Gain-of-function mutation 36
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 26
Missense Human R271P Lower cell-surface expression of channel 26
Missense Human F273L Lower cell-surface expression of channel 26
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. 4,10,27
Missense Human R269C 4,10,27
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. 4,10,27
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. 4,10,27
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. 48
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 24
Missense Human R594H Constitutively open channels 24

References

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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 et al.. (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. Doñate-Macian P, Duarte Y, Rubio-Moscardo F, Pérez-Vilaró G, Canan J, Díez J, González-Nilo F, Valverde MA. (2020) Structural determinants of TRPV4 inhibition and identification of new antagonists with antiviral activity. Br J Pharmacol, [Epub ahead of print]. [PMID:32959389]

13. 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 USA, 110 (15): 6157-62. [PMID:23530219]

14. 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]

15. 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]

16. 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 USA, 107 (44): 19084-9. [PMID:20956320]

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