Store-operated calcium entry and increased endothelial cell permeability
Store-operated calcium entry and increased endothelial cell permeability
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DOI：
10.1152/ajplung.2000.279.5.l815
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发表时间：
2000-11-01
影响因子：
4.9
通讯作者：
Stevens, T
中科院分区：
文献类型：
--
作者：
Norwood, N;Moore, TM;Stevens, T
我们假设肌球蛋白轻链激酶（MLCK）将钙释放与钙库操作的钙进入激活联系起来，这对控制内皮细胞屏障很重要。MLCK的急性抑制引起钙从三磷酸肌醇敏感的钙储存释放，并阻止随后激活的存储操作的钙进入毒胡萝卜素，这表明MLCK作为一个重要的机制连接存储耗尽激活膜钙通道。此外，在电压钳位的单个大鼠肺动脉内皮细胞，毒胡萝卜素激活的内向钙电流被MLCK抑制废除。F-肌动蛋白破坏激活钙电流，和F-肌动蛋白稳定消除thapsiglavin诱导的电流。Thapsigargin增加内皮细胞通透性的存在下，但不是在没有，细胞外钙，表明钙进入降低屏障功能的重要性。尽管MLCK抑制阻止了毒胡萝卜素刺激钙进入，但它不能阻止毒胡萝卜素增加渗透性。相反，MLCK活性的抑制增加了渗透性，这在低细胞外钙中尤其突出。总之，MLCK链接存储耗尽激活的存储操作的钙进入通道。然而，MLCK对钙进入的抑制不足以阻止毒胡萝卜素增加内皮细胞通透性。
We hypothesized that myosin light chain kinase (MLCK) links calcium release to activation of store-operated calcium entry, which is important for control of the endothelial cell barrier. Acute inhibition of MLCK caused calcium release from inositol trisphosphate-sensitive calcium stores and prevented subsequent activation of store-operated calcium entry by thapsigargin, suggesting that MLCK serves as an important mechanism linking store depletion to activation of membrane calcium channels. Moreover, in voltage-clamped single rat pulmonary artery endothelial cells, thapsigargin activated an inward calcium current that was abolished by MLCK inhibition. F-actin disruption activated a calcium current, and F-actin stabilization eliminated the thapsigargin-induced current. Thapsigargin increased endothelial cell permeability in the presence, but not in the absence, of extracellular calcium, indicating the importance of calcium entry in decreasing barrier function. Although MLCK inhibition prevented thapsigargin from stimulating calcium entry, it did not prevent thapsigargin from increasing permeability. Rather, inhibition of MLCK activity increased permeability that was especially prominent in low extracellular calcium. In conclusion, MLCK links store depletion to activation of a store-operated calcium entry channel. However, inhibition of calcium entry by MLCK is not sufficient to prevent thapsigargin from increasing endothelial cell permeability.