title: Fast and reversible stimulation of astrocytic glycolysis by K+ and a delayed and persistent effect of glutamate.
abstract: Synaptic activity is followed within seconds by a local surge in lactate concentration, a phenomenon that underlies functional magnetic resonance imaging and whose causal mechanisms are unclear, partly because of the limited spatiotemporal resolution of standard measurement techniques. Using a novel Förster resonance energy transfer-based method that allows real-time measurement of the glycolytic rate in single cells, we have studied mouse astrocytes in search for the mechanisms responsible for the lactate surge. Consistent with previous measurements with isotopic 2-deoxyglucose, glutamate was observed to stimulate glycolysis in cultured astrocytes, but the response appeared only after a lag period of several minutes. Na(+) overloads elicited by engagement of the Na(+)-glutamate cotransporter with d-aspartate or application of the Na(+) ionophore gramicidin also failed to stimulate glycolysis in the short term. In marked contrast, K(+) stimulated astrocytic glycolysis by fourfold within seconds, an effect that was observed at low millimolar concentrations and was also present in organotypic hippocampal slices. After removal of the agonists, the stimulation by K(+) ended immediately but the stimulation by glutamate persisted unabated for >20 min. Both stimulations required an active Na(+)/K(+) ATPase pump. By showing that small rises in extracellular K(+) mediate short-term, reversible modulation of astrocytic glycolysis and that glutamate plays a long-term effect and leaves a metabolic trace, these results support the view that astrocytes contribute to the lactate surge that accompanies synaptic activity and underscore the role of these cells in neurometabolic and neurovascular coupling.
authors: Centro de Estudios Científicos (CECS), Casilla 1469, Valdivia, Chile.
authors: Carla X
authors: CX
authors: Bittner
authors: Rocío
authors: R
authors: Valdebenito
authors: Iván
authors: I
authors: Ruminot
authors: Anitsi
authors: A
authors: Loaiza
authors: Valeria
authors: V
authors: Larenas
authors: Tamara
authors: T
authors: Sotelo-Hitschfeld
authors: Hans
authors: H
authors: Moldenhauer
authors: Alejandro
authors: A
authors: San Martín
authors: Robin
authors: R
authors: Gutiérrez
authors: Marilyn
authors: M
authors: Zambrano
authors: L Felipe
authors: LF
authors: Barros
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002478:Cells, Cultured; D031541:Fluorescence Resonance Energy Transfer; D018698:Glutamic Acid / Q000494:pharmacology*; D006019:Glycolysis / Q000502:physiology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011188:Potassium / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013268:Stimulation, Chemical
chemical_list: D007202:Indicators and Reagents; D018698:Glutamic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium