INVOLVEMENT OF STRETCH-ACTIVATED ION CHANNELS IN CA-2+ MOBILIZATION TO MECHANICAL STRETCH IN ENDOTHELIAL-CELLS
INVOLVEMENT OF STRETCH-ACTIVATED ION CHANNELS IN CA-2+ MOBILIZATION TO MECHANICAL STRETCH IN ENDOTHELIAL-CELLS
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DOI：
10.1152/ajpcell.1993.264.4.c1037
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发表时间：
1993-04-01
影响因子：
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通讯作者：
SOKABE, M
中科院分区：
文献类型：
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作者：
NARUSE, K;SOKABE, M
内皮细胞受到血流的剪切应力、血压的正常应力和血管扩张的拉伸。已知这些力可能通过内部钙动员诱导几种血管活性物质的分泌（R。F.福奇戈特Circ. Res. 53：557-573，1983; M. J. Peach，A. L. Loeb，H. A.歌手，和J。高血压达拉斯7，增刊I：I-94-1-100，1985）。在这里，我们报告，拉伸细胞膜增加细胞内钙离子浓度（[Ca 2 +]i）在硅膜上培养的人脐静脉内皮细胞。在施加拉伸脉冲（3-s持续时间）后，[Ca 2 +]i迅速增加，缓慢衰减。结果表明，这种增加是由于Ca ~（2+）通过牵张激活（SA）通道进入引起的：（1）当细胞外Ca ~（2+）被去除后，Ca ~（2+）反应消失，（2）阳离子选择性SA通道阻断剂Gd ~（3+）能阻断这种反应，但硝苯地平不能;和3）外部施加的Mn 2+（已知其渗透机械敏感性通道但不渗透Ca 2+通道）在施加机械拉伸后立即进入细胞内空间。[Ca 2 +]i的增加被认为是由至少两个组件：一个初始的快速组件和延迟较慢的组件。Ryanodine抑制慢成分。这表明，拉伸膜主要诱导细胞外Ca 2+通过SA通道进入，然后从细胞内Ca 2+库释放Ca 2+。
Endothelial cells are subjected to shear stresses by blood flow, normal stresses by blood pressure, and stretch by vessel expansion. These forces are known to induce secretions of several vasoactive substances probably via internal calcium mobilization (R. F. Furchgott. Circ. Res. 53: 557-573, 1983; M. J. Peach, A. L. Loeb, H. A. Singer, and J. Saye. Hypertension Dallas 7, Suppl. I: I-94-1-100, 1985.). Here we report that stretching cellular membranes increased intracellular Ca2+ concentration ([Ca2+]i) in human umbilical endothelial cells cultured on silicon membranes. Upon application of a stretch pulse (3-s duration), [Ca2+]i increased rapidly and decayed slowly. The following results suggest that this increase arises from Ca2+ entry through stretch-activated (SA) channels: 1) the Ca2+ response disappeared when extracellular Ca2+ was removed; 2) gadolinium (Gd3+), a blocker for cation-selective SA channels, blocked the response but nifedipine did not; and 3) externally applied Mn2+, which is known to permeate mechanosensitive channels but not Ca2+ channels, entered the intracellular space immediately after an application of mechanical stretch. The increase in [Ca2+]i was found to consist of at least two components: an initial fast component and a delayed slower component. Ryanodine inhibited the slow component. It is suggested that stretching the membrane primarily induced extracellular Ca2+ entry through SA channels followed by Ca2+ releases from intracellular Ca2+ stores.