Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing

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 se...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2007-04, Vol.54 (1), p.59-72
Main Authors: Shimizu, Hidetada, Watanabe, Eiji, Hiyama, Takeshi Y, Nagakura, Ayano, Fujikawa, Akihiro, Okado, Haruo, Yanagawa, Yuchio, Obata, Kunihiko, Noda, Masaharu
Format: Article
Language:English
Subjects:
Animals
Behavior
Blood-brain barrier
Brain
Brain - cytology
Brain - metabolism
Brain research
Cells, Cultured
Cloning
Enzyme Inhibitors - pharmacology
Feeding Behavior - drug effects
Feeding Behavior - physiology
Glioma
Glucose
Glucose - metabolism
Glutamate Decarboxylase - genetics
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
Isoenzymes - genetics
Lactates - metabolism
Male
Medical research
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neuroglia - drug effects
Neuroglia - metabolism
Neurons
Neurons - drug effects
Neurons - physiology
Ouabain - pharmacology
Rats
Rodents
Salt
Science
Sense Organs - cytology
Sense Organs - physiology
Signal Transduction - physiology
Sodium - metabolism
Sodium - pharmacology
Sodium Channels - deficiency
Sodium Channels - physiology
Sodium-Potassium-Exchanging ATPase - physiology
Studies
Transfection
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Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2007.03.014