School of Medicine, Department of Biomedicine, 13 Sur 2702, Colonia Volcanes, 72000 Puebla, Mexico.
Biochem Biophys Res Commun. 2010 Apr 23;395(1):126-30. doi: 10.1016/j.bbrc.2010.03.153. Epub 2010 Mar 29.
The role of Na(+)-Ca(2+) exchanger (NCX) in vascular endothelium is still matter of debate. Depending on both the endothelial cell (EC) type and the extracellular ligand, NCX has been shown to operate in either the forward (Ca(2+) out)- or the reverse (Ca(2+) in)-mode. In particular, acetylcholine (Ach) has been shown to promote Ca(2+) inflow in the intact endothelium of excised rat aorta. Herein, we assessed the involvement of NCX into the Ca(2+) signals elicited by ATP in such preparation. Removal of extracellular Na(+) (0Na(+)) causes the NCX to switch into the reverse-mode and induced an increase in intracellular Ca(2+) concentration (Ca(2+)), which disappeared in the absence of extracellular Ca(2+), and in the presence of benzamil, which blocks both modes of NCX, and KB-R 7943, a selective inhibitor of the reverse-mode. ATP induced a transient Ca(2+) signal, whose decay was significantly prolonged by 0Na(+), benzamil, DCB, and monensin while it was unaffected by KB-R 7943. Notably, lowering extracellular Na(+) concentration increased the sensibility to lower doses of ATP. These date suggest that, unlike Ach-stimulated ECs, NCX promotes Ca(2+) extrusion when the stimulus is provided by ATP in intact endothelium of rat aorta. These data show that, within the same preparation, NCX operates in both modes, depending on the chemical nature of the extracellular stimulus.
钠钙交换器（NCX）在血管内皮中的作用仍存在争议。根据内皮细胞（EC）的类型和细胞外配体，NCX 可以以正向（Ca2+外流）或反向（Ca2+内流）模式运行。特别是，乙酰胆碱（Ach）已被证明可促进大鼠离体主动脉完整内皮细胞的 Ca2+内流。在此，我们评估了 NCX 在这种制备物中对 ATP 引起的 Ca2+信号的参与。去除细胞外 Na+（0Na+）会使 NCX 切换到反向模式，并导致细胞内 Ca2+浓度增加([Ca2+]（i）），当不存在细胞外 Ca2+时，这种增加消失，而在苯甲脒、同时阻断 NCX 的两种模式的 KB-R 7943 和选择性抑制反向模式的 DCB 和莫能菌素存在的情况下，这种增加消失。ATP 诱导瞬时 Ca2+信号，0Na+、苯甲脒、DCB 和莫能菌素显著延长其衰减，而 KB-R 7943 对其无影响。值得注意的是，降低细胞外 Na+浓度可增加对较低剂量 ATP 的敏感性。这些数据表明，与 Ach 刺激的 EC 不同，当刺激来自大鼠主动脉完整内皮细胞中的 ATP 时，NCX 促进 Ca2+外排。这些数据表明，在同一制剂中，NCX 根据细胞外刺激的化学性质，以两种模式运行。
