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 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.
Shimizu
Hidetada
H
Division of Molecular Neurobiology, National Institute for Basic Biology, Okazaki, Aichi 444-8787, Japan.
Watanabe
Eiji
E
Hiyama
Takeshi Y
TY
Nagakura
Ayano
A
Fujikawa
Akihiro
A
Okado
Haruo
H
Yanagawa
Yuchio
Y
Obata
Kunihiko
K
Noda
Masaharu
M
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005910:Glioma; D005947:Glucose / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics; D007773:Lactates / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D012679:Sense Organs / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D015222:Sodium Channels / Q000172:deficiency / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D014162:Transfection
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007773:Lactates; D015222:Sodium Channels; D049452:Green Fluorescent Proteins; D010042:Ouabain; D012964:Sodium; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose