Zholos Alexander V
Department of Biophysics, Educational and Scientific Centre "Institute of Biology", Taras Shevchenko Kiev National University, Kiev, 03022, Ukraine,
Handb Exp Pharmacol. 2014;222:129-56. doi: 10.1007/978-3-642-54215-2_6.
Human canonical transient receptor potential channel 5 (TRPC5) has been cloned from the Xq23 region on chromosome X as a suspect in nonsyndromic mental retardation. TRPC5 is a Ca(2+)-permeable cation channel predominantly expressed in the CNS, including the hippocampus, cerebellum, amygdala, sensory neurons, and retina. It also shows more restricted expression in the periphery, notably in the kidney and cardiovascular system. Homotetrameric TRPC5 channels are primarily activated by receptors coupled to Gq and phospholipase C and/or Gi proteins, but TRPC5 channels may also gate in a store-dependent manner, which requires other partner proteins such TRPC1, STIM1, and Orai1. There is an impressive array of other activators of TRPC5 channels, such as nitric oxide, lysophospholipids, sphingosine-1-phosphate, reduced thioredoxin, protons, lanthanides, and calcium, and many can cause its direct activation. Moreover, TRPC5 shows constitutive activity, and it is responsive to membrane stretch and cold. Thus, TRPC5 channels have significant potential for synergistic activation and may serve as an important focal point in Ca(2+) signalling and electrogenesis. Moreover, TRPC5 functions in partnership with about 60 proteins, including TRPC1, TRPC4, calmodulin, IP3 receptors, NHERF, NCS-1, junctate, stathmin 2, Ca(2+)-binding protein 1, caveolin, and SESTD1, while its desensitisation is mediated by both protein kinases A and C. TRPC5 has a distinct voltage dependence shared only with its closest relative, TRPC4. Its unique N-shaped activation curve underlined by intracellular Mg(2+) block seems to be perfectly "shaped" to trigger action potential discharge, but not to grossly interfere with the action potential shape. The range of biological functions of TRPC5 channels is also impressive, from neurotransmission to control of axon guidance and vascular smooth muscle cell migration and contractility. Recent studies of Trpc5 gene knockouts begin to uncover its roles in fear, anxiety, seizures, and cold sensing.
人类典型瞬时受体电位通道5（TRPC5）是从X染色体Xq23区域克隆而来的，被怀疑与非综合征性智力迟钝有关。TRPC5是一种Ca(2+)可渗透的阳离子通道，主要在中枢神经系统中表达，包括海马体、小脑、杏仁核、感觉神经元和视网膜。它在外周组织中也有更局限的表达，特别是在肾脏和心血管系统中。同源四聚体TRPC5通道主要由与Gq和磷脂酶C及/或Gi蛋白偶联的受体激活，但TRPC5通道也可能以储存依赖的方式开启，这需要其他伴侣蛋白，如TRPC1、STIM1和Orai1。TRPC5通道还有一系列令人印象深刻的其他激活剂，如一氧化氮、溶血磷脂、鞘氨醇-1-磷酸、还原型硫氧还蛋白、质子、镧系元素和钙，许多都能直接激活它。此外，TRPC5具有组成性活性，并且对膜拉伸和寒冷有反应。因此，TRPC5通道具有显著的协同激活潜力，可能是Ca(2+)信号传导和电发生的重要焦点。此外，TRPC5与约60种蛋白质相互作用，包括TRPC1、TRPC4、钙调蛋白、IP3受体、NHERF、NCS-1、连接蛋白、微管相关蛋白2、Ca(2+)结合蛋白1、小窝蛋白和SESTD1，而其脱敏由蛋白激酶A和C介导。TRPC5具有独特的电压依赖性，仅与其最密切的亲属TRPC4共享。其独特的N形激活曲线在细胞内Mg(2+)阻断的作用下，似乎完美地“塑造”为触发动作电位发放，但不会严重干扰动作电位的形状。TRPC5通道的生物学功能范围也令人印象深刻，从神经传递到轴突导向的控制以及血管平滑肌细胞的迁移和收缩性。最近对Trpc5基因敲除的研究开始揭示其在恐惧、焦虑、癫痫发作和冷觉感知中的作用。
