IMMEDIATE AND DELAYED-EFFECTS OF IN-VITRO ISCHEMIA ON GLUTAMATE EFFLUX FROM GUINEA-PIG CEREBRAL-CORTEX SLICES

Immediate and delayed effects of glucose deprivation, oxygen deprivati on (hypoxia) and both oxygen and glucose deprivation (in vitro ischemi a) on glutamate efflux from guinea pig cerebral cortex slices were stu died. Immediate effects were evaluated by measuring changes of glutama te efflux during the metabolic insults. Delayed effects were evaluated by measuring the response of the tissue to a 50 mM KCl pulse applied 60 min after the metabolic insults. Deprivation of glucose in the medi um did not induce either immediate or delayed effects, while hypoxic c ondition produced an immediate slight stimulation of glutamate efflux without any delayed effect. Conversely, in vitro ischemia produced bot h immediate and delayed effects on glutamate efflux. During in vitro i schemia glutamate efflux dramatically increased in a calcium-independe nt and tetrodotoxin-sensitive manner; this effect was potentiated by a low sodium containing medium. The blockade of the sodium/potassium AT P(ase) exchanger by ouabain caused a glutamate outflow similar to that induced by in vitro ischemia. On the whole, these data demonstrate th e central role played by the sodium electrochemical gradient and by th e membrane glutamate uptake system in the glutamate overflow induced b y in vitro ischemia. Moreover, in slices previously exposed to both ox ygen and glucose deprivation the effect of KCl on glutamate efflux was potentiated. This in vitro ischemia-induced delayed potentiation of n eurotransmitter efflux, until now unreported in the literature, was fo und to be selectively restricted to glutamatergic structures and to be mainly due to an enhancement of the exocytotic component of glutamate release. (C) 1997 Elsevier Science B.V.