Abstract
Glutamate, released at a majority of excitatory synapses in the central nervous system, depolarizes neurons by acting at specific receptors. Its action is terminated by removal from the synaptic cleft mostly via Na+- dependent uptake systems located on both neurons and astrocytes. Here we report that glutamate, in addition to its receptor-mediated actions on neuronal excitability, stimulates glycolysis-i.e., glucose utilization and lactate production-in astrocytes. This metabolic action is mediated by activation of a Na+-dependent uptake system and not by interaction with receptors. The mechanism involves the Na+/K+-ATPase, which is activated by an increase in the intracellular concentration of Na+ cotransported with glutamate by the electrogenic uptake system. Thus, when glutamate is released from active synapses and taken up by astrocytes, the newly identified signaling pathway described here would provide a simple and direct mechanism to tightly couple neuronal activity to glucose utilization. In addition, glutamate-stimulated glycolysis is consistent with data obtained from functional brain imaging studies indicating local nonoxidative glucose utilization during physiological activation.
Original language | English (US) |
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Pages (from-to) | 10625-10629 |
Number of pages | 5 |
Journal | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |
Volume | 91 |
Issue number | 22 |
DOIs | |
State | Published - Oct 25 1994 |
Externally published | Yes |
Keywords
- 2-deoxyglucose
- K-ATPase
- Na
- glutamate transporter
- magnetic resonance imaging
- positron-emission tomography
ASJC Scopus subject areas
- General