Requirement of Glycogenolysis for Uptake of Increased Extracellular K+ in Astrocytes: Potential Implications for K+ Homeostasis and Glycogen Usage in Brain
Requirement of Glycogenolysis for Uptake of Increased Extracellular K+ in Astrocytes: Potential Implications for K+ Homeostasis and Glycogen Usage in Brain
复制标题
星形胶质细胞中糖原分解对吸收增加的细胞外 K 的要求：对脑中 K 稳态和糖原使用的潜在影响
DOI：
10.1007/s11064-012-0938-3
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发表时间：
2013-03-01
影响因子：
4.4
通讯作者：
Peng, Liang
中科院分区：
文献类型：
--
作者：
Xu, Junnan;Song, Dan;Peng, Liang
在神经元刺激或病理生理条件下，星形胶质细胞K+摄取对细胞外K+（[K+]e）清除的重要性越来越被认可。它通过优先刺激星形胶质细胞Na+，K+-ATP酶而发生，该酶具有比其神经元对应物更高的Km和Vmax值，在协同转运蛋白NKCC 1的额外支持下，[K+]e更高。由最近DiNuzzo等人的论文触发，我们使用糖原分解抑制剂DAB对小鼠星形胶质细胞的原代培养物进行给药，以确定K+摄取是否需要K+刺激的糖原分解。KCl增加5 mM（仅刺激Na+，K+-ATP酶）或10 mM（刺激两种转运蛋白），在含葡萄糖的盐水培养基中制备，以在添加后变为等渗。DAB完全抑制两种摄取，Na+，K+-ATP酶介导的通过阻止Na+摄取以刺激其细胞内Na+激活位点，和NKCC 1介导的通过抑制去极化和L通道介导的Ca 2+摄取。抑制参与这些过程的信号通路的药物也会抑制K+的摄取。假设类似的体内特征，部分文献数据支持，K+刺激的星形胶质细胞K+摄取必须停止后，细胞外K+正常化。这将允许Kir1.4介导的释放和由较弱的神经元Na+，K+-ATP酶再摄取。
The importance of astrocytic K+ uptake for extracellular K+ ([K+]e) clearance during neuronal stimulation or pathophysiological conditions is increasingly acknowledged. It occurs by preferential stimulation of the astrocytic Na+,K+-ATPase, which has higher Km and Vmax values than its neuronal counterpart, at more highly increased [K+]e with additional support of the cotransporter NKCC1. Triggered by a recent DiNuzzo et al. paper, we used administration of the glycogenolysis inhibitor DAB to primary cultures of mouse astrocytes to determine whether K+ uptake required K+-stimulated glycogenolysis. KCl was increased by either 5 mM (stimulating only the Na+,K+-ATPase) or 10 mM (stimulating both transporters) in glucose-containing saline media prepared to become iso-osmotic after the addition. DAB completely inhibited both uptakes, the Na+,K+-ATPase-mediated by preventing Na+ uptake for stimulation of its intracellular Na+-activated site, and the NKCC1-mediated uptake by inhibition of depolarization- and L-channel-mediated Ca2+ uptake. Drugs inhibiting the signaling pathways involved in either of these processes also abolished K+ uptake. Assuming similar in vivo characteristics, partly supported by literature data, K+-stimulated astrocytic K+ uptake must discontinue after normalization of extracellular K+. This will allow Kir1.4-mediated release and reuptake by the less powerful neuronal Na+,K+-ATPase.