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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2010-10-5
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pubmed:abstractText |
Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl(-). Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl(-) acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl(-) at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1097-4199
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
6
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pubmed:volume |
68
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
99-112
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pubmed:dateRevised |
2011-10-18
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pubmed:meshHeading |
pubmed-meshheading:20920794-4-Aminopyridine,
pubmed-meshheading:20920794-Acetoacetates,
pubmed-meshheading:20920794-Animals,
pubmed-meshheading:20920794-Astrocytes,
pubmed-meshheading:20920794-Behavior, Animal,
pubmed-meshheading:20920794-Cells, Cultured,
pubmed-meshheading:20920794-Chlorides,
pubmed-meshheading:20920794-Chromatography, High Pressure Liquid,
pubmed-meshheading:20920794-Disease Models, Animal,
pubmed-meshheading:20920794-Dopamine,
pubmed-meshheading:20920794-Dose-Response Relationship, Drug,
pubmed-meshheading:20920794-Embryo, Mammalian,
pubmed-meshheading:20920794-Excitatory Postsynaptic Potentials,
pubmed-meshheading:20920794-Exocytosis,
pubmed-meshheading:20920794-Gene Expression Regulation,
pubmed-meshheading:20920794-Glutamic Acid,
pubmed-meshheading:20920794-Hippocampus,
pubmed-meshheading:20920794-Humans,
pubmed-meshheading:20920794-Ketone Bodies,
pubmed-meshheading:20920794-Membrane Potential, Mitochondrial,
pubmed-meshheading:20920794-Mice,
pubmed-meshheading:20920794-Mice, Inbred C57BL,
pubmed-meshheading:20920794-Microdialysis,
pubmed-meshheading:20920794-Models, Biological,
pubmed-meshheading:20920794-Neurons,
pubmed-meshheading:20920794-Patch-Clamp Techniques,
pubmed-meshheading:20920794-Potassium Channel Blockers,
pubmed-meshheading:20920794-Rats,
pubmed-meshheading:20920794-Seizures,
pubmed-meshheading:20920794-Synaptic Vesicles,
pubmed-meshheading:20920794-Vesicular Glutamate Transport Protein 2
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pubmed:year |
2010
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pubmed:articleTitle |
Metabolic control of vesicular glutamate transport and release.
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pubmed:affiliation |
Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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