Dietrich A, Gudermann T
Institut für Pharmakologie u. Toxikologie, FB. Medizin, Philipps-Universität Marburg, 35033 Marburg, Germany.
Handb Exp Pharmacol. 2007(179):125-41. doi: 10.1007/978-3-540-34891-7_7.
TRPC6 is a Ca(2+)-permeable non-selective cation channel expressed in brain, smooth muscle containing tissues and kidney, as well as in immune and blood cells. Channel homomers heterologously expressed have a characteristic doubly rectifying current-voltage relationship and are six times more permeable for Ca2+ than for Na+. In smooth muscle tissues, however, Na+ influx and activation of voltage-gated calcium channels by membrane depolarization rather than Ca2+ elevation by TRPC6 channels is the driving force for contraction. TRPC6 channels are directly activated by the second messenger diacylglycerol (DAG) and regulated by specific tyrosine or serine phosphorylation. Extracellular Ca2+ has inhibitory effects, while Ca2+/calmodulin acting from the intracellular side has potentiator effects on channel activity. Given its specific expression, TRPC6 is likely to play a number of physiological roles. Studies with TRPC6(-/-) mice suggest a role for the channel in the regulation of vascular and pulmonary smooth muscle contraction. TRPC6 was identified as an essential component of the slit diaphragm architecture of kidney podocytes. Other functions in immune and blood cells, as well as in brain and in smooth muscle-containing tissues such as stomach, colon and myometrium, remain elusive.
瞬时受体电位阳离子通道蛋白6（TRPC6）是一种对钙离子通透的非选择性阳离子通道，在脑、含平滑肌的组织、肾脏以及免疫细胞和血细胞中均有表达。异源表达的通道同聚体具有特征性的双整流电流-电压关系，对钙离子的通透性比对钠离子高6倍。然而，在平滑肌组织中，钠离子内流以及膜去极化激活电压门控钙通道而非TRPC6通道引起的钙离子浓度升高才是收缩的驱动力。TRPC6通道可被第二信使二酰甘油（DAG）直接激活，并受特定酪氨酸或丝氨酸磷酸化的调节。细胞外钙离子具有抑制作用，而从细胞内侧起作用的钙离子/钙调蛋白则对通道活性有增强作用。鉴于其特定的表达情况，TRPC6可能发挥多种生理作用。对TRPC6基因敲除小鼠的研究表明，该通道在调节血管和肺平滑肌收缩中起作用。TRPC6被确定为肾足细胞裂孔隔膜结构的重要组成部分。其在免疫细胞、血细胞以及脑和含平滑肌组织（如胃、结肠和子宫肌层）中的其他功能仍不清楚。
