CHANGES IN AMINO-ACID RELEASE AND MEMBRANE-POTENTIAL DURING CEREBRAL HYPOXIA AND GLUCOSE DEPRIVATION

Excessive release of glutamate is believed to play a major role in the susceptibility of neurons to ischaemia. Whether the glutamate release is the primary event or occurs in response to electrophysiologic alte rations has not been clarified. In the present study, the amino acid r elease was therefore correlated to changes in electrophysiological par ameters and energy status during conditions of low oxygen tension and varying glucose concentrations in rat hippocampal slices. Plain hypoxi a failed to produce glutamate release. All neurons underwent, however, a slow depolarization causing most of the neurons to lose their membr ane potential within 10 minutes. By restoring the membrane potential t o resting level by current injection, the neurons could still be activ ated synaptically and respond to transmitter application. Following re oxygenation most of the cells regained their resting membrane potentia l, but showed reduced excitability. When the slices were exposed to hy poxia combined with glucose deprivation (simulated ischaemia), there w as a pronounced increase in the glutamate release. This glutamate rele ase was always preceded by a fast anoxic depolarization. Whereas hypox ia reduced the ATP content only to approximately 50%, ATP was depleted in slices exposed to simulated ischaemia. The results demonstrate tha t although the neurons lose their membrane potential completely during hypoxia, there is no glutamate release. A fast anoxic depolarization provoked by simulated ischaemia, however, is always followed by glutam ate release, probably due to a more severe ATP depletion.