NBCe1 Mediates the Acute Stimulation of Astrocytic Glycolysis by Extracellular K+
NBCe1 Mediates the Acute Stimulation of Astrocytic Glycolysis by Extracellular K+
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DOI：
10.1523/jneurosci.2310-11.2011
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发表时间：
2011-10-05
影响因子：
5.3
通讯作者：
Felipe Barros, L.
中科院分区：
文献类型：
--
作者：
Ruminot, Ivan;Gutierrez, Robin;Felipe Barros, L.
兴奋性突触传递刺激脑组织糖酵解。这种现象是FDG-PET成像中检测到的信号，并且通过增强乳酸生成，也被认为是fMRI信号的一部分。利用基于小鼠星形胶质细胞Forster共振能量转移的方法，我们最近观察到细胞外K（+）的小幅上升可以在几秒钟内刺激糖酵解b> 300%。K（+）反应被瓦巴因阻断，但细胞内Na (+)/K (+) ATP酶泵与Na（+）的结合是无效的，这表明涉及Na（+）泵和ATP消耗的典型反馈调节途径只是允许的，并且涉及另一种机制。由于星形胶质细胞具有明显的K（+）渗透性和电致Na (+)/HCO3-共转运体NBCe1的高表达，因此星形胶质细胞对细胞外K（+）升高的反应是质膜去极化和细胞内碱化。在这篇文章中，我们证明了一个快速的糖酵解反应可以独立于K（+）引起的质膜去极化或细胞内碱化。NBCe1缺失小鼠（Slc4a4）星形胶质细胞对K（+）的糖酵解反应不存在，并被NBCe1的功能或药理抑制所阻断。海马神经元在异源NBCe1表达后获得K（+）敏感糖酵解。这种现象也可以在HEK293细胞中通过NBCe1和组成性开放的K（+）通道的共表达来重建。我们得出结论，NBCe1是星形胶质细胞中连接兴奋性突触传递和糖酵解快速调节的前馈机制的关键因素。
Excitatory synaptic transmission stimulates brain tissue glycolysis. This phenomenon is the signal detected in FDG-PET imaging and, through enhanced lactate production, is also thought to contribute to the fMRI signal. Using a method based on Forster resonance energy transfer in mouse astrocytes, we have recently observed that a small rise in extracellular K (+) can stimulate glycolysis by > 300% within seconds. The K (+) response was blocked by ouabain, but intracellular engagement of the Na (+)/K (+) ATPase pump with Na (+) was ineffective, suggesting that the canonical feedback regulatory pathway involving the Na (+) pump and ATP depletion is only permissive and that a second mechanism is involved. Because of their predominant K (+) permeability and high expression of the electrogenic Na (+)/HCO3- cotransporter NBCe1, astrocytes respond to a rise in extracellular K (+) with plasma membrane depolarization and intracellular alkalinization. In the present article, we show that a fast glycolytic response can be elicited independently of K (+) by plasma membrane depolarization or by intracellular alkalinization. The glycolytic response to K (+) was absent in astrocytes from NBCe1 null mice (Slc4a4) and was blocked by functional or pharmacological inhibition of the NBCe1. Hippocampal neurons acquired K (+) -sensitive glycolysis upon heterologous NBCe1 expression. The phenomenon could also be reconstituted in HEK293 cells by coexpression of the NBCe1 and a constitutively open K (+) channel. We conclude that the NBCe1 is a key element in a feedforward mechanism linking excitatory synaptic transmission to fast modulation of glycolysis in astrocytes.