Earley Scott, Brayden Joseph E
Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada; and Department of Pharmacology, University of Vermont College of Medicine, Burlington, Vermont.
Physiol Rev. 2015 Apr;95(2):645-90. doi: 10.1152/physrev.00026.2014.
The mammalian genome encodes 28 distinct members of the transient receptor potential (TRP) superfamily of cation channels, which exhibit varying degrees of selectivity for different ionic species. Multiple TRP channels are present in all cells and are involved in diverse aspects of cellular function, including sensory perception and signal transduction. Notably, TRP channels are involved in regulating vascular function and pathophysiology, the focus of this review. TRP channels in vascular smooth muscle cells participate in regulating contractility and proliferation, whereas endothelial TRP channel activity is an important contributor to endothelium-dependent vasodilation, vascular wall permeability, and angiogenesis. TRP channels are also present in perivascular sensory neurons and astrocytic endfeet proximal to cerebral arterioles, where they participate in the regulation of vascular tone. Almost all of these functions are mediated by changes in global intracellular Ca(2+) levels or subcellular Ca(2+) signaling events. In addition to directly mediating Ca(2+) entry, TRP channels influence intracellular Ca(2+) dynamics through membrane depolarization associated with the influx of cations or through receptor- or store-operated mechanisms. Dysregulation of TRP channels is associated with vascular-related pathologies, including hypertension, neointimal injury, ischemia-reperfusion injury, pulmonary edema, and neurogenic inflammation. In this review, we briefly consider general aspects of TRP channel biology and provide an in-depth discussion of the functions of TRP channels in vascular smooth muscle cells, endothelial cells, and perivascular cells under normal and pathophysiological conditions.
哺乳动物基因组编码了阳离子通道瞬时受体电位（TRP）超家族的28个不同成员，这些成员对不同离子种类表现出不同程度的选择性。所有细胞中都存在多种TRP通道，它们参与细胞功能的多个方面，包括感觉感知和信号转导。值得注意的是，TRP通道参与调节血管功能和病理生理学，这也是本综述的重点。血管平滑肌细胞中的TRP通道参与调节收缩性和增殖，而内皮TRP通道活性是内皮依赖性血管舒张、血管壁通透性和血管生成的重要促成因素。TRP通道也存在于血管周围感觉神经元和大脑小动脉近端的星形胶质细胞终足中，它们在这些部位参与血管张力的调节。几乎所有这些功能都是由细胞内整体Ca(2+)水平的变化或亚细胞Ca(2+)信号事件介导的。除了直接介导Ca(2+)内流外，TRP通道还通过与阳离子内流相关的膜去极化或通过受体或储存操作机制影响细胞内Ca(2+)动态。TRP通道失调与血管相关疾病有关，包括高血压、新生内膜损伤、缺血再灌注损伤、肺水肿和神经源性炎症。在本综述中，我们简要考虑TRP通道生物学的一般方面，并深入讨论正常和病理生理条件下TRP通道在血管平滑肌细胞、内皮细胞和血管周围细胞中的功能。
