Excitatory Amino Acid Receptors and Depolarization‐Induced Ca2+ Influx into Hippocampal Slices

Abstract

Hippocampal brain slices were incubated with depolarizing agents or excitatory amino acids in the presence of excitatory amino acid antagonists [.omega.-phosphonic .alpha.-aminocarboxylic acids-2-amino-4-phosphonobutyric acid (AP4), 2-amino-5-phosphonovaleric acid (AP5), or 2-amino-7-phosphonoheptanoic acid (AP7)-or .gamma.-D-glutamylaminomethylsulphonic acid (GAMs)] or a calcium-channel blocker, (S)-1-(3-methyoxyphenyl)-3-methylaza-7-cyano-7-(3,4-dimethoxyphenyl)-8-methyl-nonane hydrochloride [(-)-D888]. The uptake of 45Ca2+ and the efflux of glutamate or aspartate induced by veratrine or high K+ was blocked (54-76%) by AP7 (IC50 46-250 .mu.M). AP5 and AP4 were less effective. (-)-D888(10 .mu.M) caused 100% block of evoked 45Ca2+ uptake. Uptake of 45Ca2+ induced by exogenous glutamate, aspartate, and N-methyl-D-aspartate (NMDA) was also inhibited by AP7, whereas GAMS completely blocked the action of kainate and partially blocked that of glutamate. The action of NMDA in stimulating 45Ca2+ uptake was Mg2+-sensitive, low Mg2+ levels in the incubation medium selectively enhancing the response. It is concluded that Ca2+ uptake evoked by excitatory amino acids is receptor-mediated, and that released excitatory amino acids are responsible for a large part of the action of veratrine and high K+ in stimulating 45Ca2+ uptake.