TRPV4 channel
| Channel name | TRPV41,2,3,4,5,6,7,8,9,10,11 |
| Description | Osmosensor channel |
| Other names | OTRPC4, VR-OAC, VRL-2, TRP-12 |
| Molecular information | Human unigene: Hs0.506713, chr. 12q24.1 |
| Mouse unigene: Mm0.266450, chr. 5 | |
| Associated subunits | Calmodulin |
| Functional assays | Patch-clamp, calcium imaging |
| Current | Outwardly rectifying, nonselective current |
| Conductance | 90pS |
| Ion selectivity | PNa/PCa = 1:6 |
| Activation | Osmolarity (EC50 = 270 mOsmol/l), phorbol esters, arachidonic acid, EETs, stretch |
| Inactivation | Calmodulin/Ca2+ |
| Activators | Reduced osmolarity (see “Comments”) |
| Gating inhibitors | None |
| Blockers | Ruthenium red, gadolinium, lanthanum |
| Radioligands | None |
| Channel distribution | Brain, liver, kidney, fat, heart, testis, salivary gland, trachea |
| Physiological functions | Osmolarity sensing with thermal modulation |
| Mutations and pathophysiology | Deletion of the ankyrin repeat domain blunts the response to low osmolarity solutions |
| Pharmacological significance | Not established |
| Comments | TRPV4 is not activated by store depletion |
chr., chromosome; VR-OAC, vanilloid receptor-related osmotically activated channel; EET, eicosatetraenoic acid.
↵1. Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, and Plant TD (2000) OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat Cell Biol 2:695-702
↵2. Denis CS, Sali A, Hudspeth AJ, Friedman JM, and Heller S (2000) Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 103:525-535
↵3. Mizuno A, Matsumoto N, Imai M, and Suzuki M (2003) Impaired osmotic sensation in mice lacking TRPV4. Am J Physiol Cell Physiol 285:C96-C101
↵4. Liedtke W, Tobin DM, Bargmann CI, and Friedman JM (2003) Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans. Proc Natl Acad Sci USA 100 (Suppl 2):14531-14536
↵5. Watanabe H, Vriens J, Prenen J, Droogmans G, Voets T, and Nilius B (2003) Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature (Lond) 424:434-438
↵6. Chung MK, Lee H, Mizuno A, Suzuki M, and Caterina M (2004a) TRPV3 and TRPV4 mediate warmth-evoked currents in primary mouse keratinocytes. J Biol Chem 279:21569-21575
↵7. Jia Y, Wang X, Varty L, Rizzo CA, Yang R, Correll CC, Phelps PT, Egan RW, and Hey JA (2004) Functional TRPV4 channels are expressed in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 287:L272-L278
↵8. Suzuki M, Watanabe Y, Oyama Y, Mizuno A, Kusano E, Hirao A, and Ookawara S (2003) Localization of mechanosensitive channel TRPV4 in mouse skin. Neurosci Lett 353:189-192
↵9. Tian W, Salanova M, Xu H, Lindsley JN, Oyama TT, Anderson S, Bachmann S, and Cohen DM (2004) Renal expression of osmotically responsive cation channel TRPV4 is restricted to water-impermeant nephron segments. Am J Physiol Renal Physiol 287:F17-F24
↵10. Strotmann R, Schultz G, and Plant TD (2003) Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site. J Biol Chem. 278:26541-26549
↵11. Vriens J, Watanabe H, Janssens A, Droogmans G, Voets T, and Nilius B (2003) Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc Natl Acad Sci USA 101:396-401