TRPV4
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Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4 gene, co-discovered by,[1][2] see also [3]
This gene encodes TRPV4, initially named vanilloid-receptor related osmotically activated channel (VR-OAC), and OSM9-like transient receptor potential channel, member 4 (OTRPC4),[1][2] a member of the vanilloid subfamily in the transient receptor potential (TRP) superfamily of ion channels.[3][4][5] The encoded protein is a Ca2+-permeable, nonselective cation channel that has been found involved in multiple physiologic functions, dysfunctions and also disease. It functions in the regulation of systemic osmotic pressure by the brain, in vascular function, in liver, intestinal, renal and bladder function, in skin barrier function and response of the skin to ultraviolet-B radiation, in growth and structural integrity of the skeleton, in function of joints, in airway- and lung function, in retinal and inner ear function, and in pain. The channel is activated by osmotic, mechanical and chemical cues. It also responds to thermal changes (warmth). Channel activation can be sensitized by inflammation and injury. Hereditary channelopathy mutations of TRPV4 lead to skeletal dysplasias, premature osteoarthritis, and neurological motor function disorders as a manifestation of a motor neuropathy or spinal muscle atrophy.
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Clinical significance
Mutations in the TRPV4 gene are associated with a range of disorders, including brachyolmia type 3, congenital distal spinal muscular atrophy, scapuloperoneal spinal muscular atrophy and subtype 2C of Charcot–Marie–Tooth disease.[6]
Pharmacology
A number of TRPV4 agonists and antagonists have been identified since its discovery.[7] The discovery of unselective modulators (e.g. antagonist Ruthenium Red) was followed by the apparition of more potent (agonist 4aPDD)[8] or selective (antagonist RN-1734)[9] compounds, including some with bioavailability suitable for in vivo pharmacology studies such as agonist GSK1016790A[10] (with ~10 fold selectivity vs TRPV1), and antagonists HC-067047[11] (with ~5 fold selectivity vs hERG and ~10 fold selectivity vs TRPM8) and RN-9893[12] (with ~50 fold selectivity vs TRPM8 and ~10 fold selectivity vs M1).
Interactions
TRPV4 has been shown to interact with MAP7[13] and LYN.[14]
See also
References
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- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 605427
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External links
- GeneReviews/NCBI/NIH/UW entry on Charcot-Marie-Tooth Neuropathy Type 2
- TRPV4 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
