TRPV4: MOLECULAR CONDUCTOR OF A DIVERSE ORCHESTRA

Transient receptor potential vanilloid type 4 (TRPV4) ion channels are Ca2+ permeable non-selective cation channels which exhibit a remarkable range of expression throughout the human body. TRPV4 belongs to the transient receptor potential vanilloid (TRPV) subfamily of transient receptor (TRP) cation channels. Thus far, 28 TRP channels have been identified in mammals and these have been classified on the basis of sequence homology into 6 sub-families. In addition to the TRPV sub-familly, these subfamilies comprise: the TRPC (“Canonical”); the TRPM (“Melastatin”); the TRPP (“Polycystin”); the TRPML (“Mucolipin”); and the TRPA (“Ankyrin”). The TRPV4 cation channel was first identified in 2000 and was surprising in that osmo-sensing, volume regulatory, ion channels had been previously thought to be limited to the volume-regulated anion channel (VRAC). TRPV4 was initially given different names derived from the key features observed by the denominating investigators. Thus, the channel was respectively denominated as the osmosensitive transient receptor potential channel 4 (OTRPC4), the vanilloid receptor-related osmotically activated channel (VR-OAC), the vanilloid receptor like channel 2 (VRL-2), and the transient receptor potential channel 12 (TRP12). However, by 2002, it had been appreciated that the channels thus described were, in fact, the same TRPV4 channel which is activated by a diverse range of stimuli so that it has been well-described as exhibiting “promiscuous gating behaviour”