Calò G, Sbrenna S, Bianchi C, Beani L
Institute of Pharmacology, University of Ferrara, Italy.
Brain Res. 1997 Mar 21;751(2):300-6. doi: 10.1016/s0006-8993(96)01425-4.
Immediate and delayed effects of glucose deprivation, oxygen deprivation (hypoxia) and both oxygen and glucose deprivation (in vitro ischemia) on glutamate efflux from guinea pig cerebral cortex slices were studied. Immediate effects were evaluated by measuring changes of glutamate efflux during the metabolic insults. Delayed effects were evaluated by measuring the response of the tissue to a 50 mM KCI pulse applied 60 min after the metabolic insults. Deprivation of glucose in the medium did not induce either immediate or delayed effects, while hypoxic condition produced an immediate slight stimulation of glutamate efflux without any delayed effect. Conversely, in vitro ischemia produced both immediate and delayed effects on glutamate efflux. During in vitro ischemia glutamate efflux dramatically increased in a calcium-independent and tetrodotoxin-sensitive manner; this effect was potentiated by a low sodium containing medium. The blockade of the sodium/potassium ATPase exchanger by ouabain caused a glutamate outflow similar to that induced by in vitro ischemia. On the whole, these data demonstrate the central role played by the sodium electrochemical gradient and by the membrane glutamate uptake system in the glutamate overflow induced by in vitro ischemia. Moreover, in slices previously exposed to both oxygen and glucose deprivation the effect of KCI on glutamate efflux was potentiated. This in vitro ischemia-induced delayed potentiation of neurotransmitter efflux, until now unreported in the literature, was found to be selectively restricted to glutamatergic structures and to be mainly due to an enhancement of the exocytotic component of glutamate release.
研究了葡萄糖剥夺、缺氧（低氧）以及氧和葡萄糖同时剥夺（体外缺血）对豚鼠大脑皮层切片谷氨酸外流的即时和延迟效应。通过测量代谢损伤期间谷氨酸外流的变化来评估即时效应。通过测量代谢损伤60分钟后施加的50mM氯化钾脉冲对组织的反应来评估延迟效应。培养基中葡萄糖的剥夺未引起即时或延迟效应，而低氧条件产生了对谷氨酸外流的即时轻微刺激，且无任何延迟效应。相反，体外缺血对谷氨酸外流产生了即时和延迟效应。在体外缺血期间，谷氨酸外流以钙非依赖性和河豚毒素敏感的方式显著增加；低钠培养基可增强此效应。哇巴因对钠钾ATP酶交换器的阻断导致了类似于体外缺血诱导的谷氨酸外流。总体而言，这些数据证明了钠电化学梯度和膜谷氨酸摄取系统在体外缺血诱导的谷氨酸溢出中所起的核心作用。此外，在先前暴露于氧和葡萄糖同时剥夺的切片中，氯化钾对谷氨酸外流的效应增强。这种体外缺血诱导的神经递质外流延迟增强作用，在文献中尚未报道，被发现选择性地局限于谷氨酸能结构，并且主要是由于谷氨酸释放的胞吐成分增强所致。
