Effects of kainic acid in rat brain synaptosomes: the involvement of calcium.
The effects of kainic acid were investigated in preparations of rat brain synaptosomes. It was found that kainic acid inhibited competitively the uptake of D-[3H]aspartate, with a Ki of approximately 0.3 mM. Kainic acid also caused release of two excitatory amino acid neurotransmitters, aspartate and glutamate, in a time- and concentration-dependent manner, but had no effect on the content of gamma-aminobutyric acid. Concomitant with the release of aspartate and glutamate, depolarization of the synaptosomal membrane and an increase in intracellular calcium were observed, with no measurable change in the concentration of internal sodium ions. The increase in intrasynaptosomal calcium and decrease in transmembrane electrical potential were prevented by the addition of glutamate, whereas the kainate-induced release of radioactive aspartate was substantially inhibited by lowering the concentration of calcium in the external medium. It is postulated that kainic acid reacts with a class of glutamate receptors located in a subpopulation of synaptosomes, presumably derived from the glutamatergic and aspartatergic neuronal pathways, which possesses high-affinity uptake system(s) for glutamate and/or aspartate. Activation of these receptors causes opening of calcium channels, influx of calcium into the synaptosomes, and depolarization of the synaptosomal plasma membrane with consequent release of amino acid neurotransmitters.
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008636:Mesencephalon / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D011759:Pyrrolidines; D001224:Aspartic Acid; D007608:Kainic Acid; D002118:Calcium