EFFECTS OF EXCITATORY AMINO-ACIDS ON THE OXYGEN-CONSUMPTION OF HIPPOCAMPAL SLICES FROM THE GUINEA-PIG

The effects of excitatory amino acids such as glutamate (Glu) and aspartate (Asp), and their receptor agonists, kainate (Ka), N-methyl-D-aspartate (NMDA), and quisqualate (Quis) on the neuronal activity and the oxygen consuption were investigated using hippocampal slices of the guinea pig. Bath application of these excitants elevated the amplitude of the postsynaptic field potential (PSP) to approximately 120% of the original level at low concentrations, although effective doses varied for the different excitants (Ka>NMDA>Quis>Glu>Asp). At concentrations over each effective dose the PSP was diminished and subsequently abolished. The application of Ka (1 .times. 10-8 to 1 .times. 10-6M), NMDA (1 .times. 10-8 to 1 .times. 10-4M), Quis (1 .times. 10-7 to 1 .times. 10-4M), Glu (1 .times. 10-5 to 5 .times. 10-4M), and Asp (1 .times. 10-5 to 5 .times. 10-3M) enhanced the oxygen consumption dose-dependently, to a maximum of 120-146% of the resting level (8.43 .mu.mol/g protein/min). It was notable that the initial increase in the oxygen consumption was associated with neuronal excitation and the doses of the excitants producing maximal oxygen consumption was in good agreement with those demonstrating disappearance of the PSP, probably because of massive depolarization of the neurones. The increase of the oxygen consumption and the neuronal activity induced by the excitants were specifically inhibited by their antagonists, such as glutamic acid diethylester (GDEE), DL-2-amino-5-phosphonovaleric acid (APV), and Joro spider toxin (JSTX). The present results strongly suggest that the enhancement of oxygen consumption due to the excitatory amino acids and agonists must reflect the neuronal activation induced by them.