CHARACTERIZATION OF D-ASPARTIC ACID UPTAKE BY RAT HIPPOCAMPAL SLICES AND EFFECT OF ISCHEMIC CONDITIONS

The cellular uptake of D-aspartic acid (D-Asp) as a model compound for glutamic acid transport was studied in rat hippocampal slices. D-Asp is accumulated by both Na+-dependent and Na+-independent processes in hippocampal slices, and both processes are dependent on temperature. The Na+-dependent uptake is assumed to be high in affinity (apparent K(m) = 0.17 mM), but low in capacity, whereas the Na+-independent uptake is much lower in affinity (K(m) = 2.86 mM), but higher in capacity. L-Aspartic acid, L-glutamic acid, dihydrokainic acid, and threo-3-hydroxy-DL-aspartic acid markedly inhibited the uptake of D-Asp with Na+ in the medium, whereas D-glutamic acid, glycine, and L-lysine had no significant effect. The Na+-dependent uptake of D-Asp was significantly reduced under "hypoglycemic," "anoxic," and "ischemic" conditions, whereas the Na+-independent uptake was unaffected. Metabolic inhibitors such as NaCN and ICH2COOH significantly inhibited the Na+-dependent uptake, but not the Na+-independent uptake. These results suggest that the Na+-dependent component of D-Asp transport in rat hippocampal cells is inactivated under ischemic conditions, whereas the Na+-independent component is unaffected.