Angiotensin II has acute effects on TRPC6 channels in podocytes of freshly isolated glomeruli.
Angiotensin II has acute effects on TRPC6 channels in podocytes of freshly isolated glomeruli.
复制标题
DOI：
10.1038/ki.2014.71
复制
发表时间：
2014-09
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
作者：
足细胞在蛋白尿性肾病的发病机制中的关键作用已经被确立。血管紧张素II引起足细胞去极化和细胞内钙浓度增加;阳离子TRPC通道家族的成员，特别是TRPC 6，被认为是负责钙通量的蛋白质。血管紧张素II通过TRPC通道引起钙瞬变，编码TRPC 6通道的基因突变导致局灶性节段性肾小球硬化的发生。在这里，我们研究了血管紧张素II对细胞内钙离子水平和内源性通道的新鲜分离的小鼠肾小球去囊完整的足细胞的影响。在野生型中鉴定出具有不同TRPC 6特性的离子通道，但在TRPC 6敲除小鼠中不存在。单通道电生理学分析发现，血管紧张素II急性激活本地TRPC样通道在足细胞的新鲜分离的肾小球和TRPC 6通道瞬时过表达的CHO细胞;该效应是由通道开放概率的变化介导的。血管紧张素II在野生型足细胞中引起细胞内钙瞬变，而在TRPC 6敲除的肾小球中，这种现象被钝化。Pan-TRPC抑制剂钆和SKF 96365降低了野生型肾小球上皮细胞的反应，而TRPC 6敲除动物的瞬时反应不受影响。因此，足细胞中TRPC 6通道的血管紧张素II依赖性激活可能在肾脏疾病的发展中起重要作用。
A key role for podocytes in the pathogenesis of proteinuric renal diseases has been established. Angiotensin II causes depolarization and increased intracellular calcium concentration in podocytes; members of the cation TRPC channels family, particularly TRPC6, are proposed as proteins responsible for calcium flux. Angiotensin II evokes calcium transient through TRPC channels and mutations in the gene encoding the TRPC6 channel result in the development of focal segmental glomerulosclerosis. Here we examined the effects of angiotensin II on intracellular calcium ion levels and endogenous channels in intact podocytes of freshly isolated decapsulated mouse glomeruli. An ion channel with distinct TRPC6 properties was identified in wild type, but was absent in TRPC6 knockout mice. Single channel electrophysiological analysis found that angiotensin II acutely activated native TRPC-like channels in both podocytes of freshly isolated glomeruli and TRPC6 channels transiently overexpressed in CHO cells; the effect was mediated by changes in the channel open probability. Angiotensin II evoked intracellular calcium transients in the wild type podocytes, which was blunted in TRPC6 knockout glomeruli. Pan-TRPC inhibitors gadolinium and SKF 96365 reduced the response in wild type glomerular epithelial cells, whereas the transient in TRPC6 knockout animals was not affected. Thus, angiotensin II-dependent activation of TRPC6 channels in podocytes may have a significant role in the development of kidney diseases.
登录
查看更多内容
影响因子：
3.7
作者：
Heeringa SF;Möller CC;Du J;Yue L;Hinkes B;Chernin G;Vlangos CN;Hoyer PF;Reiser J;Hildebrandt F
通讯作者：
Hildebrandt F
影响因子：
18.2
作者：
Greka A;Mundel P
通讯作者：
Mundel P
血管紧张素 II 可提高培养大鼠荚膜细胞的细胞膜钙活性
影响因子：
19.6
作者：
Henger, A;Huber, T;Pavenstadt, H
通讯作者：
Pavenstadt, H
影响因子：
5.3
作者：
Dietrich, A;Schnitzler, MMY;Birnbaumer, L
通讯作者：
Birnbaumer, L
影响因子：
15.9
作者：
Gloy, J;Henger, A;Pavenstadt, H
通讯作者：
Pavenstadt, H