Orai1 and Ca2+-independent phospholipase A2 are required for store-operated Icat-SOC current, Ca2+ entry, and proliferation of primary vascular smooth muscle cells.
Orai1 and Ca2+-independent phospholipase A2 are required for store-operated Icat-SOC current, Ca2+ entry, and proliferation of primary vascular smooth muscle cells.
复制标题
DOI：
10.1152/ajpcell.00312.2011
复制
发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Bo Yang;T. Gwóźdź;J. Dutko-Gwóźdź;V. Bolotina
中科院分区：
文献类型：
--
作者：
Bo Yang;T. Gwóźdź;J. Dutko-Gwóźdź;V. Bolotina
钙池操纵的钙内流（SOCE）对血管平滑肌细胞（SMC）的多种功能非常重要，根据其表型，SMC可以类似于兴奋性和非兴奋性细胞。与非兴奋细胞类似，Orai 1在去分化培养的SMC和平滑肌细胞系中介导Ca（2+）选择性（CRAC样）电流和SOCE。然而，Orai 1在阳离子选择性储存操纵通道（cat-SOC）中的作用仍不清楚，cat-SOC负责原发性SMC中的SOCE。在本研究中，我们重点关注原发性SMC，并评估Orai 1和Ca（2+）非依赖性磷脂酶A（2）（iPLA（2）β或PLA 2G 6）在cat-SOC电流（I（cat-SOC））、SOCE和SMC增殖激活中的作用。利用分子、电生理、成像和功能方法，我们证明了Orai 1或iPLA（2）β的分子敲低导致对原代主动脉SMC中的全细胞cat-SOC电流和SOCE的类似抑制，并导致DNA合成显著减少和SMC增殖受损。这是首次证明Orai 1和iPLA（2）β对cat-SOC、SOCE和原发性主动脉SMC增殖同样重要。
Store-operated Ca(2+) entry (SOCE) is important for multiple functions of vascular smooth muscle cells (SMC), which, depending of their phenotype, can resemble excitable and nonexcitable cells. Similar to nonexcitable cells, Orai1 was found to mediate Ca(2+)-selective (CRAC-like) current and SOCE in dedifferentiated cultured SMC and smooth muscle-derived cell lines. However, the role of Orai1 in cation-selective store-operated channels (cat-SOC), which are responsible for SOCE in primary SMC, remains unclear. Here we focus on primary SMC, and assess the role of Orai1 and Ca(2+)-independent phospholipase A(2) (iPLA(2)β, or PLA2G6) in activation of cat-SOC current (I(cat-SOC)), SOCE, and SMC proliferation. Using molecular, electrophysiological, imaging, and functional approaches, we demonstrate that molecular knockdown of either Orai1 or iPLA(2)β leads to similar inhibition of the whole cell cat-SOC current and SOCE in primary aortic SMC and results in significant reduction in DNA synthesis and impairment of SMC proliferation. This is the first demonstration that Orai1 and iPLA(2)β are equally important for cat-SOC, SOCE, and proliferation of primary aortic SMC.