Experimental ischemia induces a persistent depolarization blocked by decreased calcium and NMDA antagonists

doi:10.1016/0304-3940(89)90276-0

Neuroscience Letters

Volume 99, Issues 1–2, 24 April 1989, Pages 125-130

https://doi.org/10.1016/0304-3940(89)90276-0 Get rights and content

Abstract

Early physiological events induced by hypoxia plus low d-glucose were investigated by intracellular recording in the rat hippocampal slice. A rapid intracellular depolarization corresponded to the extracellularly recorded anoxic depolarization. This intracellular depolarization consisted of two pharmacologically distinct components, an initial depolarization and a persistent depolarization. The persistent phase of depolarization was selectively blocked by lowering calcium and raising magnesium and by $N- methyl- d -aspartate$ (NMDA) antagonists. This persistent depolarization can account for the long-term synaptic failure seen following experimental ischemia in vitro.

References (18)

M. Balestrino et al.
Chlorpromazine protects brain tissue in hypoxia by delaying spreading depression-mediated calcium influx
Brain Res.
(1986)
G.D. Clark et al.
Blockade of excitatory amino acid receptors protects anoxic hippocampal slices
Neuroscience
(1987)
H. Collewijn et al.
Membrane potential of cerebral cortical cells during spreading depression and asphyxia
Exp. Neurol.
(1966)
D.W.G. Cox et al.
On the relationship between the excitability of dentate granule cell field potentials and their sensitivity to low glucose
Brain Res.
(1988)
A.H. Ganong et al.
Kynurenic acid inhibits synaptic and acidic amino acid-induced responses in the rat hippocampus and spinal cord
Brain Res.
(1983)
B. Meldrum et al.
Ischaemic brain damage: the role of excitatory activity and of calcium entry
Br. J. Anaesth.
(1985)
E.L. Roberts et al.
Recovery of synaptic transmission predicted from extracellular K⁺ undershoots following brief anoxia in hippocampal slices
Brain Res.
(1987)
T.J. Sick et al.
Extracellular potassium ion activity and electrophysiology in the hippocampal slice: paradoxical recovery of synaptic transmission during anoxia
Brain Res.
(1987)
N. Fujiwara et al.
Effects of hypoxia on rat hippocampal neurons in vitro
J. Physiol. (Lond.)
(1987)

There are more references available in the full text version of this article.

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Experimental ischemia induces a persistent depolarization blocked by decreased calcium and NMDA antagonists

Abstract

Brain Res.

Neuroscience

Exp. Neurol.

Brain Res.

Brain Res.

Br. J. Anaesth.

Brain Res.

Brain Res.

Effects of hypoxia on rat hippocampal neurons in vitro

J. Physiol. (Lond.)