Department of Molecular Cell Biology, Laboratory Ion Channel Research, Campus Gasthuisberg, KULeuven, Herestraat 49, bus 802, B-3000 Leuven, Belgium.
Prog Biophys Mol Biol. 2010 Sep;103(1):2-17. doi: 10.1016/j.pbiomolbio.2009.10.002. Epub 2009 Oct 14.
The Transient Receptor Potential Vanilloid 4 channel, TRPV4, is a Ca(2+) and Mg(2+) permeable non-selective cation channel involved in many different cellular functions. It is activated by a variety of physical and chemical stimuli, including heat, mechano-stimuli, endogenous substances such as arachidonic acid and its cytochrome P450-derived metabolites (epoxyeicosatrienoic acids), endocannabinoids (anandamide and 2-arachidonoylglycerol), as well as synthetic alpha-phorbol derivatives. Recently, TRPV4 has been characterized as an important player modulating osteoclast differentiation in bone remodelling and as a urothelial mechanosensor that controls normal voiding. Several TRPV4 gain-of-function mutations are shown to cause autosomal-dominant bone dysplasias such as brachyolmia and Koszlowski disease. In this review we comprehensively describe the structural, biophysical and (patho)physiological properties of the TRPV4 channel and we summarize the current knowledge about the role of TRPV4 in the pathogenesis of several diseases.
瞬时受体电位香草酸 4 型通道（TRPV4）是一种 Ca2+和 Mg2+通透性非选择性阳离子通道，参与多种不同的细胞功能。它可以被多种物理和化学刺激激活，包括热、机械刺激、内源性物质如花生四烯酸及其细胞色素 P450 衍生代谢物（环氧二十碳三烯酸）、内源性大麻素（大麻素和 2-花生四烯酰甘油）以及合成的α-佛波醇衍生物。最近，TRPV4 被认为是调节骨重塑中破骨细胞分化的重要参与者，也是控制正常排尿的尿路上皮机械感受器。一些 TRPV4 功能获得性突变会导致常染色体显性骨发育不良，如短肢畸形和 Koszlowski 病。在这篇综述中，我们全面描述了 TRPV4 通道的结构、生物物理和（病理）生理学特性，并总结了 TRPV4 在几种疾病发病机制中的作用的现有知识。
