Djali S, Dawson L A
Neuroscience Research, Wyeth Ayerst, Princeton, NJ 08543-8000, USA.
Neurochem Res. 2001 Feb;26(2):135-43. doi: 10.1023/a:1011094728469.
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.
使用叠氮化钠（NaN₃）诱导的缺氧加无糖血症作为化学诱导缺血的模型，我们已经对从体外灌流海马切片中内源性释放的兴奋性和抑制性氨基酸进行了表征。化学缺血导致叠氮化物（1 - 30 mM）剂量依赖性地增加谷氨酸、天冬氨酸和GABA的外流。通过去除Ca²⁺，或添加电压依赖性Na⁺通道阻滞剂河豚毒素（TTX）、选择性Ca²⁺通道阻滞剂芋螺毒素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被减弱。同样，添加GLT - 1谷氨酸转运抑制剂二氢海因酸（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，化学缺血诱导的氨基酸外流增加似乎既源于神经元池，通过传统的胞吐释放，也源于胶质细胞来源，通过GLT - 1转运体的逆转和阴离子通道调节的细胞肿胀。
