Effects of Kainic Acid in Rat Brain Synaptosomes: The Involvement of Calcium

Abstract

The effects of kainic acid were investigated in preparations of rat brain synaptosomes. Kainic acid inhibited competitively the uptake of D-[3H]aspartate, with a Ki of .apprx. 0.3 mM. Kainic acid also caused release of 2 excitatory amino acid neurotransmitters, aspartate and glutamate, in a time- and concentration-dependent manner, but had no effect on the GABA content. Concomitant with the release of aspartate and glutamate, depolarization of the synaptosomal membrane and an increase in intracellular Ca were observed, with no measurable change in the concentration of internal Na+. The increase in intrasynaptosomal Ca 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 Ca in the external medium. Kainic acid probably reacts with a class of glutamate receptors located in a subpopulatoin of synaptosomes, presumably derived from the glutamatergic and aspartatergic neurnal pathways, which possess high-affinity uptake system(s) for glutamate and/or aspartate. Activation of these receptors causes opening of Ca channels, influx of Ca into the synaptosomes and depolarization of the synaptosomal plasma membrane with consequent release of amino acid neurotransmitters.