Cytosolic-free calcium and neurotransmitter release with decreased availability of glucose or oxygen.
Exposing brain slices to reduced oxygen tensions or impairing their ability to utilize oxygen with KCN decreases acetylcholine (ACh) but increases dopamine (DA) and glutamate in the medium at the end of a release incubation. To determine if these changes are due to alterations in the presynaptic terminals, release from isolated nerve endings (i.e. synaptosomes) was determined during histotoxic hypoxia (KCN). KCN reduced potassium-stimulated synaptosomal ACh release and increased dopamine and glutamate release. Since several lines of evidence suggest that altered calcium homeostasis underlies these changes in release, the effects of reducing medium calcium concentrations from 2.3 to 0.1-mM were determined. In low calcium medium, KCN still increased dopamine and glutamate release, but had no effect on ACh release. Hypoxia increased cytosolic-free calcium in both the normal and low calcium medium, although the elevation was less in the low calcium medium. Thus, the effects of histotoxic hypoxia on cytosolic free calcium concentration paralleled those on glutamate and dopamine release. Reducing the glucose concentration of the medium also increased cytosolic-free calcium. The data are consistent with the hypothesis that hypoxia and hypoglycemia increase cytosolic-free calcium, which stimulates the release of dopamine and glutamate, whose excessive release may lead to subsequent cellular damage postsynaptically.
Gibson
G E
GE
Cornell University Medical College, Burke Rehabilitation Center, White Plains, New York 10605.
Manger
T
T
Toral-Barza
L
L
Freeman
G
G
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000493:pharmacokinetics*; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000493:pharmacokinetics*; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*
D018377:Neurotransmitter Agents; D005947:Glucose; D002118:Calcium