Mechanism of glutamate release from rat hippocampal slices during in vitro ischemia

被引:90
作者
Roettger, V
Lipton, P
机构
[1] UNIV WISCONSIN,DEPT PHYSIOL,MADISON,WI 53706
[2] UNIV WISCONSIN,CTR NEUROSCI,MADISON,WI 53706
关键词
glutamate; Na+-dependent transport; dihydrokainate; transporter-mediated release; veratridine; cerebral ischemia;
D O I
10.1016/0306-4522(96)00314-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
There was a large release of endogenous glutamate and of pre-accumulated [H-3]-D-aspartate from rat hippocampal slices during deprivation of oxygen and glucose (in vitro ischemia). The role of Na+-dependent glutamate transporters in this process was investigated. The release of both glutamate and [H-3]-D-aspartate was largely blocked by two competitive substrate analogues of the Na+-dependent glutamate transporters (L-trans-pyrrolidine-2,4-dicarboxylate and D,L-threo-B-hydroxyaspartate) if the substrate analogues were intracellularly loaded prior to the ischemia. The pre-loaded analogue, D,L-threo-B-hydroxyaspartate, did not block exocytotic release of glutamate, induced by high-potassium. Dihydrokainate, an inhibitor of a subset of the Na+-dependent transporters, did not inhibit ischemia-induced release of glutamate or [H-3]-D-aspartate. However, it did block release induced by veratridine, which was also blocked by the pre-loaded substrate analogues. Dihydrokainate could still inhibit veratridine-induced release during ischemia, showing that conditions during ischemia did not reduce its efficacy. It is concluded that release of glutamate during ischemia is largely via reversal of the Na+-dependent glutamate transport system. The differential effects of dihydrokainate and the competitive substrate analogues on ischemia-induced release indicate that this release occurs via a subset of the glutamate transporters that are present in the hippocampus. Copyright (C) 1996 IBRO.
引用
收藏
页码:677 / 685
页数:9
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