Non-Canonical Control of Neuronal Energy Status by the Na+ Pump
Non-Canonical Control of Neuronal Energy Status by the Na+ Pump
复制标题
DOI：
10.1016/j.cmet.2018.11.005
复制
发表时间：
2019-03-05
期刊：
影响因子：
29
通讯作者：
Felipe Barros, L.
中科院分区：
文献类型：
--
作者：
Baeza-Lehnert, Felipe;Saab, Aiman S.;Felipe Barros, L.
神经元具有有限的细胞内能量储存，但经历能量需求的急剧和不可预测的增加。为了更好地了解这些细胞如何在不经历代谢应激的情况下反复从静息状态过渡到活跃状态，我们使用离子敏感探针和FRET传感器在体外和体内监测了它们对神经传递的早期代谢反应。短θ脉冲触发立即Na+进入，随后延迟刺激Na+/K+ ATP酶泵。出乎意料的是，胞质ATP和ADP水平在广泛的生理工作量范围内不受干扰，揭示了Na+泵和线粒体之间的严格通量耦合。代谢通量的测量结果显示，丙酮酸盐的线粒体的“启动”阶段，而葡萄糖的消耗与延迟的Na+泵刺激相一致。实验表明，Na+泵在线粒体ATP合成和糖酵解中起着重要作用。我们的结论是，神经元的能量稳态介导的腺嘌呤核苷酸或Ca 2+，但由Na+泵命令的机制。
Neurons have limited intracellular energy stores but experience acute and unpredictable increases in energy demand. To better understand how these cells repeatedly transit from a resting to active state without undergoing metabolic stress, we monitored their early metabolic response to neurotransmission using ion-sensitive probes and FRET sensors in vitro and in vivo. A short theta burst triggered immediate Na+ entry, followed by a delayed stimulation of the Na+/K+ ATPase pump. Unexpectedly, cytosolic ATP and ADP levels were unperturbed across a wide range of physiological workloads, revealing strict flux coupling between the Na+ pump and mitochondria. Metabolic flux measurements revealed a "priming'' phase of mitochondrial energization by pyruvate, whereas glucose consumption coincided with delayed Na+ pump stimulation. Experiments revealed that the Na+ pump plays a permissive role for mitochondrial ATP production and glycolysis. We conclude that neuronal energy homeostasis is not mediated by adenine nucleotides or by Ca2+, but by a mechanism commanded by the Na+ pump.