Inorganic phosphate enhances phosphonucleotide concentrations in cultured fetal rat cortical neurons

Our laboratory has recently characterized saturable Na +-dependent P i import into cultured fetal rat cortical neurons and shown that a substantial fraction of the P i so accumulated is incorporated into ATP. We now report that the ATP, NADPH and intracellular free P i ([P i] i) concentrations of cultured fetal rat cortical neurons are dependent on the extracellular P i concentration ([P i] e). [ATP], [NADPH] and [P i] i display a hyperbolic dependence upon [P i] e, being significantly increased after incubation with [P i] e of ≥10 μM, and maximal at ≥500 μM. Increases in both [ATP] and [NADPH] are abolished in the absence of glucose. In the absence of extracellular P i, both [ATP] and [P i] i decline over time. Our data suggest that in cultured fetal rat cortical neurons [P i] e has a direct effect on glucose utilization, stimulating both ATP and NADPH synthesis via glycolysis and the pentose phosphate pathway.