Effects of domoate, glutamate and glucose deprivation on calcium uptake by rat brain tissue in vitro

Abstract

The toxic effects of excitatory amino acids (EAAs) on the central nervous system appear to be mediated by calcium. Calcium uptake into rat brain tissue slices was studied in the absence and in the presence of domoate and glutamate. Calcium uptake into brain cytoplasm was enhanced by domoate in a concentration-dependent manner. Glutamate also stimulated calcium uptake. Calcium uptake into brain tissue was enhanced markedly by the removal of glucose from the Krebs-Henseleit-Ringer bicarbonate incubation medium. Stimulation of calcium uptake by glucose deprivation increased with incubation time, suggesting the depletion of energy stores, i.e. ATP, which is necessary for calcium transport in brain tissue. Replacement of NaCl with choline chloride in the incubation medium also enhanced calcium uptake into brain tissue cytosol. The removal of both glucose and NaCl from the medium produced an additive effect on calcium uptake, indicating independent mechanisms of action. NaF stimulated calcium uptake into brain tissue more in the presence of glucose than in its absence. Since NaF is an inhibitor of glucose metabolism, these results indicate that glucose metabolism is somehow linked to calcium transport in brain tissue. Since ATP is required by calcium pumps, which extrude as well as store calcium in nervous tissue cells, depletion of ATP, either in the absence of glucose or when glucose metabolism is blocked by NaF, may be responsible for the accumulation of calcium in the brain tissue cytosol, and for the neurotoxicity induced by domoate and glutamate.