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

Hidetada Shimizu; Eiji Watanabe; Takeshi Y Hiyama; Ayano Nagakura; Akihiro Fujikawa; Haruo Okado; Yuchio Yanagawa; Kunihiko Obata; Masaharu Noda

doi:10.1016/j.neuron.2007.03.014

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

Neuron. 2007 Apr 5;54(1):59-72. doi: 10.1016/j.neuron.2007.03.014.

Authors

Hidetada Shimizu¹, Eiji Watanabe, Takeshi Y Hiyama, Ayano Nagakura, Akihiro Fujikawa, Haruo Okado, Yuchio Yanagawa, Kunihiko Obata, Masaharu Noda

Affiliation

¹ Division of Molecular Neurobiology, National Institute for Basic Biology, Okazaki, Aichi 444-8787, Japan.

PMID: 17408578
DOI: 10.1016/j.neuron.2007.03.014

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / cytology
Brain / metabolism*
Cells, Cultured
Enzyme Inhibitors / pharmacology
Feeding Behavior / drug effects
Feeding Behavior / physiology
Glioma
Glucose / metabolism
Glutamate Decarboxylase / genetics
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Isoenzymes / genetics
Lactates / metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neuroglia / drug effects
Neuroglia / metabolism*
Neurons / drug effects
Neurons / physiology*
Ouabain / pharmacology
Rats
Sense Organs / cytology
Sense Organs / physiology
Signal Transduction / physiology*
Sodium / metabolism*
Sodium / pharmacology
Sodium Channels / deficiency
Sodium Channels / physiology*
Sodium-Potassium-Exchanging ATPase / physiology
Transfection

Substances

Enzyme Inhibitors
Isoenzymes
Lactates
Sodium Channels
Green Fluorescent Proteins
Ouabain
Sodium
Glutamate Decarboxylase
glutamate decarboxylase 1
Sodium-Potassium-Exchanging ATPase
Glucose