EFFECTS OF GLUTAMATE-RECEPTOR AGONISTS AND ANTAGONISTS ON CA2+ UPTAKEIN RAT HIPPOCAMPAL SLICES LESIONED BY GLUCOSE DEPRIVATION OR BY KAINATE

The functional relevance of presynaptic glutamate receptors in control ling presynaptic Ca2+ influx and thereby transmitter release is unknow n. To test if presynaptic Ca2+ entry in the hippocampus is controlled by glutamate autoreceptors, we created a hippocampal slice preparation for investigation of presynaptic Ca2+ signals with Ca2+-sensitive mic roelectrodes after lesioning of neurons by glucose deprivation or kain ate. Stratum radiatum and alveus stimulation-induced postsynaptic fiel d potential components were irreversibly abolished in areas CAI and CA 3 of lesioned slices, whereas stratum radiatum stimulation still evoke d afferent volleys. Repetitive stimulation of the stratum radiatum sti ll induced decreases in extracellular Ca2+ concentration. Repetitive s timulation of the alveus no longer induced decreases in extracellular Ca2+ concentration, suggesting complete damage of pyramidal cells. The stratum radiatum stimulation-induced decreases in extracellular Ca2concentration in lesioned slices were comparable to those elicited dur ing application of the glutamate antagonists 6-cyano-7-nitroquinoxalin e-2,3-dione and L-2-amino-5-phosphonovalerate. In lesioned slices the stimulus-induced presynaptic Ca2+ influx was reversibly reduced by kai nate, pha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), N-met hyl-D-aspartate and glutamate without effects on afferent volleys. The kainate and N-methyl-D-aspartate effects on presynaptic Ca2+ signals were partly sensitive to dihydroxy-6-nitro-7-sulphamoyl-benzo(f)quinox aline and L-2-amino-5-phosphonovalerate, respectively, while the AMPA effects were not significantly affected by 2,3-dihydroxy-6-nitro-7-sul phamoyl-benzo suggesting involvement of a novel glutamate receptor sub type. The involvement of a novel glutamate receptor subtype was suppor ted by our findings that ionotropic glutamate receptor agonists also r educe presynaptic Ca2+ influx under conditions of blocked synaptic tra nsmission by 6-cyano-7-nitroquinoxaline-2,3-dione and L-2-amino-5-phos phonovalerate. 1-Aminocyclopentane-trans-1,3-dicarboxylic acid had no significant effect on presynaptic Ca2+ entry. Also, the presynaptic Ca 2+ influx was not influenced by the glutamate receptor antagonists 6-c yano-7-nitroquinoxaline-2,3-dione, -dihydroxy-6-nitro-7-sulphamoylbenz o(f)quinoxaline and L-2-amino-5-phosphonovalerate when applied alone. Low kainate concentrations (5 mu M) reduced presynaptic Ca2+ signals i n area CA3 but not in area CA1; demonstrating the higher affinity of p resynaptic kainate receptors on messy fibre terminals. Copyright (C) 1 997 IBRO.