EFFECTS OF DOMOATE, GLUTAMATE AND GLUCOSE DEPRIVATION ON CALCIUM-UPTAKE BY RAT-BRAIN TISSUE IN-VITRO

The toxic effects of excitatory amino acids (EAAs) on the central nerv ous system appear to be mediated by calcium. Calcium uptake into rat b rain tissue slices was studied in the absence and in the presence of d omoate and glutamate. Calcium uptake into brain cytoplasm was enhanced by domoate in a concentration-dependent manner. Glutamate also stimul ated calcium uptake. Calcium uptake into brain tissue was enhanced mar kedly by the removal of glucose from the Krebs-Henseleit-Ringer bicarb onate incubation medium. Stimulation of calcium uptake by glucose depr ivation increased with incubation time, suggesting the depletion of en ergy stores, i.e. ATP, which is necessary for calcium transport in bra in tissue. Replacement of NaCl with choline chloride in the incubation medium also enhanced calcium uptake into brain tissue cytosol. The re moval of both glucose and NaCl from the medium produced an additive ef fect on calcium uptake, indicating independent mechanisms of action. N aF stimulated calcium uptake into brain tissue more in the presence of glucose than in its absence. Since NaF is an inhibitor of glucose met abolism, these results indicate that glucose metabolism is somehow lin ked to calcium transport in brain tissue. Since ATP is required by cal cium pumps, which extrude as well as store calcium in nervous tissue c ells, depletion of ATP, either in the absence of glucose or when gluco se metabolism is blocked by NaF, may be responsible for the accumulati on of calcium in the brain tissue cytosol, and for the neurotoxicity i nduced by domoate and glutamate.