Inhibition of the high-affinity glutamate uptake system facilitates the massive potassium flux during cerebral ischaemia in vivo.
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.