Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Neurochem Int. 2010 Dec;57(7):783-94. doi: 10.1016/j.neuint.2010.08.016. Epub 2010 Sep 15.
Astrocytes and NG2 glia respond to CNS injury by the formation of a glial scar. Since the changes in K(+) currents in astrocytes and NG2 glia that accompany glial scar formation might influence tissue outcome by altering K(+) ion homeostasis, we aimed to characterize the changes in K(+) currents in hippocampal astrocytes and NG2 glia during an extended time window of reperfusion after ischemic injury. Global cerebral ischemia was induced in adult rats by bilateral, 15-min common carotid artery occlusion combined with low-pressure oxygen ventilation. Using the patch-clamp technique, we investigated the membrane properties of hippocampal astrocytes and NG2 glia in situ 2 hours, 6 hours, 1 day, 3 days, 7 days or 5 weeks after ischemia. Astrocytes in the CA1 region of the hippocampus progressively depolarized starting 3 days after ischemia, which coincided with decreased Kir4.1 protein expression in the gliotic tissue. Other K(+) channels described previously in astrocytes, such as Kir2.1, Kir5.1 and TREK1, did not show any changes in their protein content in the hippocampus after ischemia; however, their expression switched from neurons to reactive astrocytes, as visualized by immunohistochemistry. NG2 glia displayed increased input resistance, decreased membrane capacitance, increased delayed outwardly rectifying and A-type K(+) currents and decreased inward K(+) currents 3 days after ischemia, accompanied by their proliferation. Our results show that the membrane properties of astrocytes after ischemia undergo complex alterations, which might profoundly influence the maintenance of K(+) homeostasis in the damaged tissue, while NG2 glia display membrane currents typical of proliferating cells.
星形胶质细胞和 NG2 神经胶质细胞通过形成神经胶质瘢痕来响应中枢神经系统损伤。由于伴随神经胶质瘢痕形成的星形胶质细胞和 NG2 神经胶质细胞中 K(+)电流的变化可能通过改变 K(+)离子稳态来影响组织结局，我们旨在表征缺血性损伤后再灌注延长时间窗内海马星形胶质细胞和 NG2 神经胶质细胞中 K(+)电流的变化。通过双侧、15 分钟的颈总动脉闭塞联合低氧通气，在成年大鼠中诱导全脑缺血。使用膜片钳技术，我们在缺血后 2 小时、6 小时、1 天、3 天、7 天或 5 周原位研究海马星形胶质细胞和 NG2 神经胶质细胞的膜特性。缺血后 3 天，海马 CA1 区的星形胶质细胞逐渐去极化，这与胶质组织中 Kir4.1 蛋白表达减少相一致。先前在星形胶质细胞中描述的其他 K(+)通道，如 Kir2.1、Kir5.1 和 TREK1，其在缺血后海马中的蛋白含量没有任何变化；然而，它们的表达通过免疫组织化学从神经元切换到反应性星形胶质细胞。NG2 神经胶质细胞表现出更高的输入电阻、更低的膜电容、更高的延迟外向整流和 A 型 K(+)电流以及更低的内向 K(+)电流，这与它们的增殖有关。我们的研究结果表明，缺血后星形胶质细胞的膜特性发生了复杂的变化，这可能会深刻影响损伤组织中 K(+)稳态的维持，而 NG2 神经胶质细胞表现出增殖细胞的典型膜电流。
