title: Inhibition of the high-affinity glutamate uptake system facilitates the massive potassium flux during cerebral ischaemia in vivo.
abstract: 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.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hirota
authors.forename: Y
authors.initials: Y
authors.lastname: Katayama
authors.forename: T
authors.initials: T
authors.lastname: Kawamata
authors.forename: T
authors.initials: T
authors.lastname: Kano
authors.forename: T
authors.initials: T
authors.lastname: Tsubokawa
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D017551:Microdialysis; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018698:Glutamic Acid; C020889:dihydrokainic acid; D011188:Potassium; D007608:Kainic Acid