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 alterations has not been clarified. In the present study, the amino acid release was therefore correlated to changes in electrophysiological parameters and energy status during conditions of low oxygen tension and varying glucose concentrations in rat hippocampal slices. Plain hypoxia failed to produce glutamate release. All neurons underwent, however, a slow depolarization causing most of the neurons to lose their membrane potential within 10 minutes. By restoring the membrane potential to resting level by current injection, the neurons could still be activated synaptically and respond to transmitter application. Following reoxygenation most of the cells regained their resting membrane potential, but showed reduced excitability. When the slices were exposed to hypoxia combined with glucose deprivation (simulated ischaemia), there was a pronounced increase in the glutamate release. This glutamate release was always preceded by a fast anoxic depolarization. Whereas hypoxia reduced the ATP content only to approximately 50%, ATP was depleted in slices exposed to simulated ischaemia. The results demonstrate that 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 glutamate release, probably due to a more severe ATP depletion.
Berg-Johnsen
J
J
Institute for Surgical Research, National Hospital, Oslo, Norway.
Grøndahl
T O
TO
Langmoen
I A
IA
Haugstad
T S
TS
Hegstad
E
E
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D008564:Membrane Potentials; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000596:Amino Acids; D001224:Aspartic Acid; D018698:Glutamic Acid; D005947:Glucose