Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing
Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing
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DOI：
10.1016/j.neuron.2007.03.014
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发表时间：
2007-04-05
期刊：
影响因子：
16.2
通讯作者：
Noda, Masaharu
中科院分区：
文献类型：
--
作者：
Shimizu, Hidetada;Watanabe, Eiji;Noda, Masaharu
钠（Na）稳态对生命至关重要，体液中的Na水平在大脑中不断监测。穹窿下器官（SFO）是负责控制盐摄入行为的感觉中心，其中Na-x通道作为Na水平传感器在特定的胶质细胞中表达。在这里，我们显示Na-x通道和Na+/K+-ATP酶的α亚基之间的直接相互作用，这带来了神经胶质细胞的代谢状态的Na依赖性激活。在野生型小鼠的SFO中观察到导致大量乳酸产生的代谢增强，但在Na-x敲除小鼠中没有观察到。此外，乳酸，以及钠，刺激GABA能神经元的活动在SFO。这些结果表明，在体液中的Na水平的生理增加的信息所感知的神经胶质细胞中的Na-x的传递到神经元的乳酸作为一种介质来调节神经活动的SFO。
Sodium (Na) homeostasis is crucial for life, and Na levels in body fluids are constantly monitored in the brain. The subfornical organ (SFO) is the center of the sensing responsible for the control of salt-intake behavior, where Na-x channels are expressed in specific glial cells as the Na-level sensor. Here, we show direct interaction between Na-x channels and alpha subunits of Na+/K+-ATPase, which brings about Na-dependent activation of the metabolic state of the glial cells. The metabolic enhancement leading to extensive lactate production was observed in the SFO of wild-type mice, but not of the Na-x-knockout mice. Furthermore, lactate, as well as Na, stimulated the activity of GABAergic neurons in the SFO. These results suggest that the information on a physiological increase of the Na level in body fluids sensed by Na-x in glial cells is transmitted to neurons by lactate as a mediator to regulate neural activities of the SFO.