Effects of hypoxia and hypoglycaemia on DC potentials recorded from the gerbil hippocampus in vitro.
The acute effects of hypoxia and/or hypoglycaemia on DC potentials recorded from CA1 pyramidal neurones of the gerbil hippocampal slice maintained in vitro were investigated. Depolarizing potential changes were recorded when the slice was superfused with the excitatory amino acid agonists: NMDA (N-methyl-D-aspartic acid; 3-30 microM), AMPA ((RS)alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate; 1-30 microM), kainate (3-100 microM) and L-glutamate (1-10 mM). In response to a 20 min period of superfusion with an hypoxic artificial CSF solution at 30 degrees C, a transient depolarization occurred followed by a marked hyperpolarization. A further hyperpolarization occurred when superfusion of the slice with an oxygenated artificial CSF recommenced. Post-hypoxia, when the neurones had repolarized, the response to NMDA (10 microM) was less than the pre-hypoxic response. The extent of the depression of the NMDA response was found to depend on three variables: a) the duration of the period of hypoxia, b) the glucose concentration of the artificial CSF, and c) the temperature of the slice. As the duration of hypoxia was increased, the depression of the NMDA response was more marked. Reduction of the glucose concentration from 11 mM to 2 mM by partial substitution with sucrose (9 mM) made the tissues more sensitive to the effects of hypoxia, whereas reduction of the temperature from 30 degrees C to 20 degrees C made them less sensitive. The depression of the response to NMDA was observed over a range of concentrations of NMDA. The concentration response curve for AMPA was also flattened, however, the depolarizations in response to kainate or GABA were preserved.(ABSTRACT TRUNCATED AT 250 WORDS)
Rogers
H
H
Department of Neuropharmacology, Glaxo Group Research, Ware, Herts., UK.
Birch
P J
PJ
Hayes
A G
AG
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D015687:Cell Hypoxia / Q000502:physiology*; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D007003:Hypoglycemia / Q000503:physiopathology*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D007051:Ibotenic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid