EVIDENCE AGAINST HIGH EXTRACELLULAR GLUTAMATE PROMOTING THE ELICITATION OF SPREADING DEPRESSION BY POTASSIUM

This study ascertains whether high extracellular glutamate contributes to the initiation of spreading depression (SD) by K+. Two microdialys is probes, each incorporating an electrode to record the extracellular direct current (DC) potential at the elicitation site, were implanted symmetrically in the cortex of anesthetized rats. Recurrent SD was tr iggered by perfusion of 130 mM K+ through the microdialysis probe for 20 min. On one side, this medium was supplemented with increasing conc entrations of glutamate (0.1-1 mM) or of the selective glutamate uptak e inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (L-trans-PDC; 1-10 m M). The effects of L-trans-PDC on extracellular glutamate and basal DC potential were studied in separate experiments. Application of K+ for 20 min consistently elicited five to seven waves of SD. Increasing th e concentration of glutamate in the perfusion medium did not alter SD elicitation. Application of L-trans-PDC concentration dependently incr eased the dialysate levels of glutamate (by similar to 19-fold with 10 mM L-trans-PDC) but, unexpectedly, reduced SD elicitation. These data do not support the hypothesis that SD is elicited because high extrac ellular glutamate resulting from exocytosis and/or reversal of glutama te uptake depolarizes adjacent neurons. As SD elicitation requires act ivation of N-methyl-D-aspartate (NMDA) receptors, these results also i llustrate that sensitivity of a pathological or experimental event to NMDA receptor antagonists does not necessarily imply involvement of in creased extracellular glutamate. This does not rule out a selective ac tion of glutamate, transiently released from presynaptic vesicles, on immediately juxtaposed postsynaptic receptors.