Second Messenger-Operated Calcium Entry Through TRPC6
Second Messenger-Operated Calcium Entry Through TRPC6
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DOI：
10.1007/978-3-319-26974-0_10
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Rosado, Juan A.
中科院分区：
文献类型：
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作者：
Bouron, Alexandre;Chauvet, Sylvain;Rosado, Juan A.
典型的瞬时受体潜力6(TRPC6)蛋白组装成形成非选择性阳离子通道的异多聚体结构。此外，许多与TRPC6相互作用的蛋白质已被鉴定，如一些酶、通道、泵、细胞骨架相关蛋白、免疫亲和素或胆固醇结合蛋白，这表明TRPC6参与了大分子复合体的形成。根据细胞类型和实验条件的不同，TRPC6的活性被报道为由不同的模式控制。例如，第二信使二酰甘油、储存-耗竭、植物提取物金丝桃素或过氧化氢都被证明触发TRPC6通道的开放。TRPC6激活的一个明显后果是胞浆内钙离子浓度升高。后一种反应可以反映钙离子通过开放的TRPC6通道进入，但它也可能是由于钠/钙交换(以反向模式运行)或电压门控钙通道(响应TRPC6介导的去极化而重新招募)所致。尽管TRPC6在许多组织和细胞类型中控制着一系列不同的生物学功能，但其病理生理功能远未被完全了解。本章介绍了TRPC6的一些关键特征，特别强调了它们在肾脏和血细胞中的生物学意义。
Canonical transient receptor potential 6 (TRPC6) proteins assemble into heteromultimeric structures forming non-selective cation channels. In addition, many TRPC6-interacting proteins have been identified like some enzymes, channels, pumps, cytoskeleton-associated proteins, immunophilins, or cholesterol-binding proteins, indicating that TRPC6 are engaged into macromolecular complexes. Depending on the cell type and the experimental conditions used, TRPC6 activity has been reported to be controlled by diverse modalities. For instance, the second messenger diacylglycerol, store-depletion, the plant extract hyperforin or H2O2 have all been shown to trigger the opening of TRPC6 channels. A well-characterized consequence of TRPC6 activation is the elevation of the cytosolic concentration of Ca2+. This latter response can reflect the entry of Ca2+ through open TRPC6 channels but it can also be due to the Na+/Ca2+ exchanger (operating in its reverse mode) or voltage-gated Ca2+ channels (recruited in response to a TRPC6-mediated depolarization). Although TRPC6 controls a diverse array of biological functions in many tissues and cell types, its pathophysiological functions are far from being fully understood. This chapter covers some key features of TRPC6, with a special emphasis on their biological significance in kidney and blood cells.