Active mitochondria surrounding the pancreatic acinar granule region prevent spreading of inositol trisphosphate-evoked local cytosolic Ca2+ signals
Active mitochondria surrounding the pancreatic acinar granule region prevent spreading of inositol trisphosphate-evoked local cytosolic Ca2+ signals
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DOI：
10.1093/emboj/18.18.4999
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发表时间：
1999-09-15
期刊：
影响因子：
11.4
通讯作者：
Petersen, OH
中科院分区：
文献类型：
--
作者：
Tinel, H;Cancela, JM;Petersen, OH
激动剂诱发的小鼠胰腺腺泡细胞胞浆Ca ~（2+）峰特异性地起始于顶端分泌极，并且主要局限于该区域。用线粒体特异性荧光染料MitoTracker绿色和罗丹明123，这些细胞器显示为主要集中在分泌颗粒区域周围的明亮带。我们使用钙敏感荧光（Fura 2）和电生理同时成像来测试两种不同类型的线粒体抑制剂对胞浆Ca 2+浓度的影响。当在释放Ca 2+的信使肌醇1，4，5-三磷酸（IP 3）存在下应用羰基氰化物间氯苯腙（CCCP）时，颗粒区的局部重复性Ca ~（2+）反应转化为细胞内Ca ~（2+）浓度的整体升高。在不存在IP 3的情况下，CCCP对胞浆Ca 2+水平没有影响。抗霉素和抗霉素+寡霉素具有与CCCP相同的作用，活性线粒体，战略性地放置在分泌极周围，阻止Ca ~（2+）从顶极富含颗粒区的初级Ca ~（2+）释放位点向含核细胞的基部扩散。当线粒体功能受到抑制时，这种屏障消失，Ca 2+信号遍布整个细胞质。
Agonist-evoked cytosolic Ca2+ spikes in mouse pancreatic acinar cells are specifically initiated in the apical secretory pole and are mostly confined to this region, The role played by mitochondria in this process has been investigated. Using the mitochondria-specific fluorescent dyes MitoTracker Green and Rhodamine 123, these organelles appeared as a bright belt concentrated mainly around the secretory granule area. We tested the effects of two different types of mitochondrial inhibitor on the cytosolic Ca2+ concentration using simultaneous imaging of Ca2+-sensitive fluorescence (Fura 2) and electrophysiology, When carbonyl cyanide m-chlorophenylhydrazone (CCCP) was applied in the presence of the Ca2+-releasing messenger inositol 1,4,5-trisphosphate (IP3), the local repetitive Ca2+ responses in the granule area were transformed into a global rise in the cellular Ca2+ concentration. In the absence of IP3, CCCP had no effect on the cytosolic Ca2+ levels. Antimycin and antimycin + oligomycin had the same effect as CCCP, Active mitochondria, strategically placed around the secretory pole, block Ca2+ diffusion from the primary Ca2+ release sites in the granule-rich area in the apical pole to the basal part of the cell containing the nucleus. When mitochondrial function is inhibited, this barrier disappears and the Ca2+ signals spread all over the cytosol.