期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 39, 期 3, 页码 513-523出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X17737012
关键词
Organotypic hippocampal slices; FRET-nanosensors; neuronal activity; astrocyte metabolism; NBCe1
资金
- Deutsche Forschungsgemeinschaft [DE 231/25-1]
- Fondecyt [3160131, 1160317]
- Chilean Government through the Centers of Excellence Base Financing Program of CONICYT
The potassium ion, K+, a neuronal signal that is released during excitatory synaptic activity, produces acute activation of glucose consumption in cultured astrocytes, a phenomenon mediated by the sodium bicarbonate cotransporter NBCe1 (SLC4A4). We have explored here the relevance of this mechanism in brain tissue by imaging the effect of neuronal activity on pH, glucose, pyruvate and lactate dynamics in hippocampal astrocytes using BCECF and FRET nanosensors. Electrical stimulation of Schaffer collaterals produced fast activation of glucose consumption in astrocytes with a parallel increase in intracellular pyruvate and biphasic changes in lactate. These responses were blocked by TTX and were absent in tissue slices prepared from NBCe1-KO mice. Direct depolarization of astrocytes with elevated extracellular K+ or Ba2+ mimicked the metabolic effects of electrical stimulation. We conclude that the glycolytic pathway of astrocytes in situ is acutely sensitive to neuronal activity, and that extracellular K+ and the NBCe1 cotransporter are involved in metabolic crosstalk between neurons and astrocytes. Glycolytic activation of astrocytes in response to neuronal K+ helps to provide an adequate supply of lactate, a metabolite that is released by astrocytes and which acts as neuronal fuel and an intercellular signal.
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