INORGANIC P-I INCREASES NEURONAL SURVIVAL IN THE ACUTE EARLY PHASE FOLLOWING EXCITOTOXIC OXIDATIVE INSULTS/

Inorganic phosphate (P-i) plays a vital role in intracellular energy m etabolism. its many effects include stimulation of glucose use, enhanc ement of high-energy phosphate concentrations, and modulation of cytos olic free [Ca2+]. Cultured fetal rat cortical neurons constitutively i mport P-i, and cytosolic levels positively correlate with [ATP], [NADP H], and energy charge. In the present study, we demonstrate that the c oncentration of intracellular P-i is an important determinant of acute neuronal survival after an excitotoxic or oxidative insult to culture d fetal rat cortical neurons. Extracellular P-i dose-dependently enhan ced survival of cortical neurons after exposure to NMDA at early (less than or equal to 6 h) time points after termination of the insult. P- i similarly increased neuronal survival after exposure to kainic acid or H2O2. P-i-exposed neurons had higher basal intracellular [P-i], [AT P], and [GSH], and slightly lower cytosolic free [Ca2+], compared with P-i-deprived neurons. Pi-exposed neurons maintained increased [ATP] a fter exposure to NMDA and displayed reduced formation of reactive oxyg en species after exposure to kainic acid or H2O2, compared with P-i-de prived neurons. These findings demonstrate that changes in extracellul ar and intracellular P-i can affect neuronal survival after excitotoxi c or oxidative insults.