Ammonia, Like K+, Stimulates the Na+, K+, 2 Cl− Cotransporter NKCC1 and the Na+,K+-ATPase and Interacts with Endogenous Ouabain in Astrocytes
Ammonia, Like K+, Stimulates the Na+, K+, 2 Cl− Cotransporter NKCC1 and the Na+,K+-ATPase and Interacts with Endogenous Ouabain in Astrocytes
复制标题
DOI：
10.1007/s11064-014-1352-9
复制
发表时间：
2014-06
影响因子：
4.4
通讯作者：
L. Hertz;Liang Peng;D. Song
中科院分区：
文献类型：
--
作者：
L. Hertz;Liang Peng;D. Song
肝性脑病或急性肝功能衰竭期间以及脑缺血后的脑水肿具有多因素病因，但由于大脑被封闭在坚硬的颅骨中，因此它是一种危险且偶尔危及生命的并发症。缺血时细胞外K？浓度增加到非常高的水平，当能量在再灌注过程中变得可用时，刺激NKCC 1，一种由Na？K？- ATP酶和积累Na？，K？和2 Cl-与水一起。这在病理条件下诱导明显的星形胶质细胞肿胀，但NKCC 1也可能在正常脑功能期间被激活，尽管程度较低。离子和水在胞外和胞内相之间的重新分布不会产生脑水肿，这另外需要穿过血脑屏障的摄取。在肝性脑病和急性肝功能衰竭的一个关键因素是K？NH4？不仅对NKCC 1和Na？K？- ATP酶和Na？，K？-内源性哇巴因的ATP酶诱导信号传导。这些反过来又激活ROS和亚硝基活性剂的产生，这些活性剂缓慢地使NKCC 1敏感，解释了为什么细胞肿胀和脑水肿通常在高氨血症条件下延迟，尽管非常高的氨浓度可以引起立即的NKCC 1激活。
Brain edema during hepatic encephalopathy or acute liver failure as well as following brain ischemia has a multifactorial etiology, but it is a dangerous and occasionally life-threatening complication because the brain is enclosed in the rigid skull. During ischemia the extracellular K? concentration increases to very high levels, which when energy becomes available during reperfusion stimulate NKCC1, a cotransporter driven by the transmembrane ion gradients established by the Na?, K?-ATPase and accumulating Na?, K? and 2 Cl-together with water. This induces pronounced astrocytic swelling under pathologic conditions, but NKCC1 is probably also activated, although to a lesser extent, during normal brain function. Redistribution of ions and water between extra-and intracellular phases does not create brain edema, which in addition requires uptake across the bloodbrain barrier. During hepatic encephalopathy and acute liver failure a crucial factor is the close resemblance between K? and NH4? in their effects not only on NKCC1 and Na?, K?-ATPase but also on Na?, K?-ATPase-induced signaling by endogenous ouabains. These in turn activate production of ROS and nitrosactive agents which slowly sensitize NKCC1, explaining why cell swelling and brain edema generally are delayed under hyperammonemic conditions, although very high ammonia concentrations can cause immediate NKCC1 activation.