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Molecular Mechanisms of TRPV4 Gating Heller S; O'Neil RGTRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades-/-Frontiers in Neuroscience 2007[]; ä (ä): äTRPV4, the fourth member of the vanilloid subfamily of TRP channels, is a calcium-permeable cation channel that is detectable in both sensory and nonsensory cells. It has been shown to be widely expressed, including in kidneys, lungs, hearts, brains, endothelial cells, and dorsal root and trigeminal sensory ganglia. The channel is characterized by multimodal activation properties that implicate it in a broad range of functions from osmoregulation to thermosensing. Although TRPV4 was originally identified as an osmotically activated channel [1-3], recent evidence demonstrates that the channel can be activated by diverse stimuli including hypoosmotic swelling [1-3], shear stress [4], nonnoxious temperatures [5,6], acidity [7], phorbol esters (both protein kinase C-activating and nonactivating phorbol esters) [4,8,9], and downstream metabolites of arachidonic acid (epoxyeicosatrienoic acids) [10,11]. The mechanism(s) underlying TRPV4 activation by these differing modalities remain(s) poorly understood. However, new evidence points to some common pathways of activation by these diverse stimuli that may underlie the apparent broad range of functions associated with the channel.ä |
