Journal
NEUROCHEMICAL RESEARCH
Volume 34, Issue 5, Pages 807-818Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-008-9833-3
Keywords
Glycolysis; Energy metabolism; Neurotransmitter; Refilling; VGLUT; Nerve terminal
Categories
Funding
- National Institutes of Health [RO1 NS 42200, RO1 MH 071384]
- Taisho Pharmaceutical Co., Ltd. ( Tokyo, Japan)
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Glucose metabolism is essential for normal brain function and plays a vital role in synaptic transmission. Recent evidence suggests that ATP synthesized locally by glycolysis, particularly via glyceraldehyde 3-phosphate dehydrogenase/3-phosphoglycerate kinase, is critical for synaptic transmission. We present evidence that ATP generated by synaptic vesicle-associated pyruvate kinase is harnessed to transport glutamate into synaptic vesicles. Isolated synaptic vesicles incorporated [H-3]glutamate in the presence of phosphoenolpyruvate (PEP) and ADP. Pyruvate kinase activators and inhibitors stimulated and reduced PEP/ADP-dependent glutamate uptake, respectively. Membrane potential was also formed in the presence of pyruvate kinase activators. ATP-trapping experiments using hexokinase and glucose suggest that ATP produced by vesicle-associated pyruvate kinase is more readily used than exogenously added ATP. Other neurotransmitters such as GABA, dopamine, and serotonin were also taken up into crude synaptic vesicles in a PEP/ADP-dependent manner. The possibility that ATP locally generated by glycolysis supports vesicular accumulation of neurotransmitters is discussed.
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