Uptake, release, and metabolism of citrate in neurons and astrocytes in primary cultures.

Synthesis, uptake, release, and oxidative metabolism of citrate were investigated in neurons and astrocytes cultured from cerebral cortex or cerebellum. In addition, the possible role of citrate as a donor of the carbon skeleton for biosynthesis of neurotransmitter glutamate was studied. All cell types expressed the enzyme citrate synthase at a high activity, the cerebellar granule neurons containing the enzyme at a higher activity than that found in the astrocytes from the two brain regions or the cortical neurons. Saturable citrate uptake could not be detected in any of the cell types, but the astrocytes, and, in particular, those of cerebellar origin, had a very active de novo synthesis and release of citrate (approximately 70 nmol x h-1 x mg of protein-1). The rate of release of citrate from neurons was < 5% of this value. Using [14C]citrate it could be shown that citrate was oxidatively metabolized to 14CO2 at a modest rate (approximately 1 nmol x h-1 x mg-1 of protein) with slightly higher rates in astrocytes compared with neurons. Experiments designed to investigate the ability of exogenously supplied citrate to serve as a precursor for synthesis of transmitter glutamate in cerebellar granule neurons failed to demonstrate this. Rather than citrate serving this purpose it may be suggested that astrocytically released citrate may regulate the extracellular concentration of Ca2+ and Mg2+ by chelation, thereby modulating neuronal excitability.