Characterization of endogenous amino acid efflux from hippocampal slices during chemically-induced ischemia
Characterization of endogenous amino acid efflux from hippocampal slices during chemically-induced ischemia
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DOI：
10.1023/a:1011094728469
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发表时间：
2001-02-01
影响因子：
4.4
通讯作者：
Dawson, LA
中科院分区：
文献类型：
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作者：
Djali, S;Dawson, LA
使用钠（NaN3）诱导的缺氧加血糖症作为化学诱导的缺血模型，我们表征了灌注海马切片中兴奋性和抑制性氨基酸的内源性释放。化学缺血导致谷氨酸、天冬氨酸和 GABA 的流出量出现叠氮化物 (1-30 mM) 剂量依赖性增加。通过去除 Ca2+，或添加电压依赖性 Na+ 通道阻断剂河豚毒素 (TTX)、选择性 Ca2+ 通道阻断剂芋螺毒素 MVIIA、MVIIC 和硝苯地平、NMDA 拮抗剂 MK801、AMPA 拮抗剂 GYKI-52466，这些增加在不同程度上减弱。同样，添加 GLT-1 谷氨酸转运抑制剂二氢红藻氨酸 (DHK) 和抗雌激素/阴离子通道阻滞剂他莫昔芬也减弱了谷氨酸和 GABA 的外流。因此，化学缺血引起的氨基酸流出的增加似乎源自神经元池（通过传统的胞吐释放）和神经胶质源（通过逆转 GLT-1 转运蛋白和阴离子通道调节的细胞肿胀）。
Using sodium (NaN3)-induced anoxia plus aglycaemia as a model of chemically-induced ischemia, we have characterized the endogenous release of excitatory and inhibitory amino acids from superfused hippocampal slices. Chemical ischemia produced an azide (1-30 mM) dose-dependent increase in the efflux of glutamate, aspartate and GABA. These increases were attenuated to varying degrees by removal of Ca2+, or the addition of the voltage dependent Na+-channel blocker tetrodotoxin (TTX), the selective Ca2+ channel blockers conotoxin MVIIA, MVIIC, and nifedipine, the NMDA antagonist MK801, the AMPA antagonist GYKI-52466. Similarly, addition of the GLT-1 glutamate transport inhibitor dihydrokainate (DHK) and the anti-estrogen/anion channel blocker tamoxifen also attenuated the efflux of glutamate and GABA. It would therefore appear that the increases in amino acid efflux induced by chemical ischemia originates from both the neuronal pool, via conventional exocytotic release, and glial sources via reversal of the GLT-1 transporter and anion channel regulated cell swelling.