Noll T, Muhs A, Besselmann M, Watanabe H, Piper H M
Physiologisches Institut I, Heinrich-Heine-Universität, Düsseldorf, Germany.
Am J Physiol. 1995 Apr;268(4 Pt 2):H1462-70. doi: 10.1152/ajpheart.1995.268.4.H1462.
How the initiation of energy depletion affects macromolecule permeability of a barrier of coronary endothelial cells was investigated. Cultured monolayers of adult rat coronary endothelial cells were exposed to 5 mM KCN and 5 mM 2-deoxy-D-glucose (2-DG). Transendothelial flux of albumin, cellular ATP content, and cytosolic Ca2+ concentration were monitored. Within the first minute, a merely partial loss (28%) of ATP reserves provoked a distinct increase (41%) in albumin flux. Rise of permeability was dependent on Ca2+ release from a thapsigargin- and ATP-sensitive endogenous store, and hyperpermeability was greatly attenuated when energy depletion was extremely rapid, as under sequential addition of 20 mM 2-DG and 5 mM KCN. Attenuation of hyperpermeability could also be achieved by use of 5-20 mM 2,3-butanedione monoxime, an inhibitor of actin-myosin interaction. This finding, together with dependence on Ca2+ and availability of residual energy, indicates that the rapid initiation of hyperpermeability is caused by a contractile mechanism.
研究了能量耗竭的起始如何影响冠状动脉内皮细胞屏障的大分子通透性。将成年大鼠冠状动脉内皮细胞的培养单层暴露于5 mM氰化钾和5 mM 2-脱氧-D-葡萄糖（2-DG）中。监测白蛋白的跨内皮通量、细胞ATP含量和细胞质Ca2+浓度。在第一分钟内，仅ATP储备的部分损失（28%）就引发了白蛋白通量的显著增加（41%）。通透性的增加取决于从毒胡萝卜素和ATP敏感的内源性储存中释放Ca2+，并且当能量耗竭极其迅速时，如在依次添加20 mM 2-DG和5 mM氰化钾的情况下，高通透性会大大减弱。使用5-20 mM 2,3-丁二酮单肟（一种肌动蛋白-肌球蛋白相互作用的抑制剂）也可以实现高通透性的减弱。这一发现，连同对Ca2+的依赖性和残余能量的可用性，表明高通透性的快速起始是由一种收缩机制引起的。
