Hirota H, Katayama Y, Kawamata T, Kano T, Tsubokawa T
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
Neurol Res. 1995 Apr;17(2):94-6. doi: 10.1080/01616412.1995.11740294.
During cerebral ischaemia, the extracellular concentration of K+ ([K+]e) increases abruptly to 50-60 mM following an initial slow increase to 6-10 mM. We have recently shown that the increase in [K+]e is significantly delayed by in situ administration of kynurenic acid, a broad spectrum antagonist of excitatory amino acids, suggesting that the catastrophic ionic fluxes occurring during ischaemia are initially mediated by EAA-coupled ion channels. In order to confirm further the role of EAAs, the changes in extracellular K+ ([K+]e) and glutamate ([Glu]e) during cerebral ischaemia were determined in the rat hippocampus by microdialysis in vivo, and the effect of dihydrokainate (DHKA), an inhibitor of the high-affinity uptake system of EAAs, was examined by in situ administration through the dialysis probe. DHKA induced a significant increase in baseline [Glu]e and facilitated the abrupt increase in [K+]e during cerebral ischaemia. These findings support the hypothesis that EAAs play a vital role in producing the rapid ionic shifts earlier during cerebral ischaemia.
在脑缺血期间，细胞外钾离子浓度（[K⁺]e）最初缓慢升高至6 - 10 mM，随后会突然升高至50 - 60 mM。我们最近发现，通过原位给予犬尿喹啉酸（一种兴奋性氨基酸的广谱拮抗剂），[K⁺]e的升高会显著延迟，这表明缺血期间发生的灾难性离子通量最初是由兴奋性氨基酸偶联离子通道介导的。为了进一步证实兴奋性氨基酸的作用，通过体内微透析测定大鼠海马体在脑缺血期间细胞外钾离子（[K⁺]e）和谷氨酸（[Glu]e）的变化，并通过透析探针原位给药来研究兴奋性氨基酸高亲和力摄取系统的抑制剂二氢卡因酸（DHKA）的作用。DHKA导致基线[Glu]e显著升高，并促进了脑缺血期间[K⁺]e的突然升高。这些发现支持了兴奋性氨基酸在脑缺血早期产生快速离子变化中起重要作用的假说。
