Excitatory amino acid receptors and depolarization-induced Ca2+ influx into hippocampal slices.
Hippocampal brain slices were incubated with depolarizing agents or excitatory amino acids either alone or 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-methoxyphenyl)-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 microM). AP5 and AP4 were less effective. (-)-D888 (10 microM) 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.
D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology; D008564:Membrane Potentials; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D014702:Veratrine / Q000494:pharmacology
D000596:Amino Acids; D007473:Ion Channels; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D014702:Veratrine; D011188:Potassium; D002118:Calcium