PDF(Pubmed)
Abstract：
In physiological conditions, the intracellular chloride concentration is much lower than the extracellular. As GABAA channels are permeable to anions, the reversal potential of GABAA is very close to that of Cl-, which is the most abundant free anion in the intra- and extracellular spaces. Intracellular chloride is regulated by the activity ratio of NKCC1 and KCC2, two chloride-cation cotransporters that import and export Cl-, respectively. Due to the closeness between GABAA reversal potential and the value of the resting membrane potential in most neurons, small changes in intracellular chloride have a major functional impact, which makes GABAA a uniquely flexible signaling system. In most neurons of the adult brain, the GABAA reversal potential is slightly more negative than the resting membrane potential, which makes GABAA hyperpolarizing. Alterations in GABAA reversal potential are a common feature in numerous conditions as they are the consequence of an imbalance in the NKCC1-KCC2 activity ratio. In most conditions (including Alzheimer\'s disease, schizophrenia, and Down\'s syndrome), GABAA becomes depolarizing, which causes network desynchronization and behavioral impairment. In other conditions (neonatal inflammation and neuropathic pain), however, GABAA reversal potential becomes hypernegative, which affects behavior through a potent circuit deactivation.
摘要：
在生理条件下,细胞内氯化物浓度远低于细胞外氯化物浓度。由于GABAA通道可透过阴离子，GABAA的反转潜力非常接近Cl-，是细胞内和细胞外空间中最丰富的游离阴离子。细胞内氯化物受NKCC1和KCC2的活性比调节，这两种导入和导出Cl-的氯化物阳离子共转运蛋白，分别。由于GABAA逆转电位与大多数神经元的静息膜电位值之间的紧密关系，细胞内氯化物的微小变化具有主要的功能影响，这使得GABAA成为一个独特灵活的信号系统。在成人大脑的大多数神经元中，GABAA逆转电位比静息膜电位略负，这使得GABAA超极化。GABAA逆转电位的变化是许多条件下的共同特征，因为它们是NKCC1-KCC2活性比失衡的结果。在大多数情况下（包括阿尔茨海默病，精神分裂症,和唐氏综合症)，GABAA变得去极化，导致网络不同步和行为损害。在其他情况下（新生儿炎症和神经性疼痛），然而,GABAA逆转电位变为超负,通过有效的电路停用来影响行为。
