Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1
Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1
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DOI：
10.1007/s00424-007-0314-3
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发表时间：
2007-12-01
影响因子：
4.5
通讯作者：
Gudermann, Thomas
中科院分区：
文献类型：
--
作者：
Dietrich, Alexander;Kalwa, Hermann;Gudermann, Thomas
在经典的瞬时受体电位(TRPC)亚家族中，TRPC1被认为是一种机械敏感型和储备型通道，被认为是由低渗细胞膨胀和吸管正压激活的，并受细胞内钙库的充盈状态调节。然而，通过对TRPC1缺陷小鼠模型的分析，可能最有说服力地获得TRPC1的生理作用的证据。因此，我们培育并分析了TRPC1(-/-)小鼠。TRPC1(-/-)小鼠对压力引起的脑动脉收缩没有影响。经低渗肿胀和吸管正压激活的脑血管平滑肌细胞，其阳离子电流与野生型细胞相比无明显差异。此外，从胸主动脉和脑动脉分离的TRPC1(-/-)小鼠的平滑肌细胞，与野生型小鼠的细胞相比，在thapsigargin、1，4，5-三磷酸肌醇和环片亚硝酸诱导的储备型阳离子内流中没有变化。与这些结果相反，减少基质相互作用分子1(STIM1)表达的小干扰RNA抑制了thapsigargin诱导的存储操作阳离子内流，表明STIM1和TRPC1是相互独立的。这些发现还暗示，与目前的概念相反，TRPC1不是血管平滑肌细胞中储存操作和拉伸激活的离子通道复合体的必备成分。
Among the classical transient receptor potential (TRPC) subfamily, TRPC1 is described as a mechanosensitive and store-operated channel proposed to be activated by hypoosmotic cell swelling and positive pipette pressure as well as regulated by the filling status of intracellular Ca2+ stores. However, evidence for a physiological role of TRPC1 may most compellingly be obtained by the analysis of a TRPC1-deficient mouse model. Therefore, we have developed and analyzed TRPC1(-/-) mice. Pressure-induced constriction of cerebral arteries was not impaired in TRPC1(-/-) mice. Smooth muscle cells from cerebral arteries activated by hypoosmotic swelling and positive pipette pressure showed no significant differences in cation currents compared to wild-type cells. Moreover, smooth muscle cells of TRPC1(-/-) mice isolated from thoracic aortas and cerebral arteries showed no change in store-operated cation influx induced by thapsigargin, inositol-1,4,5 trisphosphate, and cyclopiazonic acid compared to cells from wild-type mice. In contrast to these results, small interference RNAs decreasing the expression of stromal interaction molecule 1 (STIM1) inhibited thapsigargin-induced store-operated cation influx, demonstrating that STIM1 and TRPC1 are mutually independent. These findings also imply that, as opposed to current concepts, TRPC1 is not an obligatory component of store-operated and stretch-activated ion channel complexes in vascular smooth muscle cells.