Gibson G E, Manger T, Toral-Barza L, Freeman G
Cornell University Medical College, Burke Rehabilitation Center, White Plains, New York 10605.
Neurochem Res. 1989 May;14(5):437-43. doi: 10.1007/BF00964858.
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.
将脑片置于低氧环境中，或用氰化钾（KCN）损害其利用氧气的能力，会使乙酰胆碱（ACh）减少，但在释放孵育结束时，会使培养基中的多巴胺（DA）和谷氨酸增加。为了确定这些变化是否是由于突触前终末的改变所致，在组织中毒性缺氧（KCN）期间，测定了分离的神经末梢（即突触体）的释放情况。KCN降低了钾刺激的突触体乙酰胆碱释放，并增加了多巴胺和谷氨酸释放。由于有几条证据表明，释放的这些变化的基础是钙稳态的改变，因此测定了将培养基钙浓度从2.3 mM降至0.1 mM的影响。在低钙培养基中，KCN仍增加多巴胺和谷氨酸释放，但对乙酰胆碱释放没有影响。缺氧使正常和低钙培养基中的胞质游离钙增加，尽管在低钙培养基中升高幅度较小。因此，组织中毒性缺氧对胞质游离钙浓度的影响与对谷氨酸和多巴胺释放的影响相似。降低培养基中的葡萄糖浓度也会增加胞质游离钙。这些数据与以下假设一致：缺氧和低血糖会增加胞质游离钙，从而刺激多巴胺和谷氨酸的释放，其过度释放可能会导致突触后细胞的后续损伤。
