| Literature DB >> 20920794 |
Narinobu Juge1, John A Gray, Hiroshi Omote, Takaaki Miyaji, Tsuyoshi Inoue, Chiaki Hara, Hisayuki Uneyama, Robert H Edwards, Roger A Nicoll, Yoshinori Moriyama.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2010 PMID： 20920794 PMCID： PMC2978156 DOI： 10.1016/j.neuron.2010.09.002
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 18.688