COMPARISON OF EFFECTS INDUCED BY TOXIC APPLICATIONS OF KAINATE AND GLUTAMATE AND BY GLUCOSE DEPRIVATION ON AREA CA1 OF RAT HIPPOCAMPAL SLICES

Baseline and stimulus-induced changes in [Ca2+](o) and [K+](o) as well as field potentials (fp's) were studied during application of the exc itatory amino acids kainate or glutamate, or during glucose deprivatio n in area CA1 and CA3 of rat hippocampal slices. Bath application of k ainate in concentrations of 1, 2, 5, 8 and 10 mM induced a sudden rapi d fall of [Ca2+](o) in area CA1, associated with a negative shift of t he slow fp. Kainate induced disappearance of stratum radiatum (SR) as well as alveus stimulation-evoked postsynaptic fp's, with partial reco very after application of up to 2 mM kainate, but no recovery after 5 mM kainate. Only afferent volleys and repetitive SR stimulation-induce d decreases of [Ca2+](o) recovered after 5 mM kainate. Similar observa tions were made with glutamate. Only when glutamate was applied with 2 0 mM, irreversible disappearance of postsynaptic fp's was noted. Gluco se deprivation for 60-90 min led to an initial slow decline of [Ca2+]( o) in area CA1 and CA3, associated with increases in [K+](o), but no s ignificant changes in the fp baseline. Before reaching the lowest leve l in [Ca2+](o), stimulation of afferent and efferent fibres in area CA 1 and CA3 evoked epileptiform discharges. After reaching the lowest le vel in [Ca2+](o), all postsynaptic potential components were irreversi bly abolished, sparing afferent volleys and SR stimulation-induced dec reases in [Ca2+](o). The application of the glutamate receptor antagon ists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 30 mu M) and L-2-amin o-5-phosphonovalerate (2APV, 30 mu M) during glucose deprivation did n ot prevent irreversible loss of alveus and SR stimulation-induced post synaptic signals. These findings suggest that glutamate release during glucose deprivation is not the main factor of acute cell damage.