NON-VESICULAR RELEASE OF GLUTAMATE FROM GLIAL-CELLS BY REVERSED ELECTROGENIC GLUTAMATE UPTAKE

GLUTAMATE uptake into nerve and glial cells usually functions to keep the extracellular glutamate concentration low in the central nervous system1. But one component of glutamate release from neurons is calcium-independent, suggesting a non-vesicular release that may be due to a reversal of glutamate uptake2,3. The activity of the electrogenic glutamate uptake carrier can be monitored by measuring the membrane current it produces4, and uptake is activated by intracellular potassium ions5. Here we report that raising the potassium concentration around glial cells evokes an outward current component produced by reversed glutamate uptake. This current is activated by intracellular glutamate and sodium, inhibited by extracellular glutamate and sodium, and increased by membrane depolarization. These results demonstrate a non-vesicular mechanism for the release of glutamate from glial cells and neurons. This mechanism may contribute to the neurotoxic rise in extracellular glutamate concentration during brain anoxia. © 1990 Nature Publishing Group.