Effects of intrastriatal injection of quinolinic acid on electrical activity and extracellular ion concentrations in rat striatum in vivo.

Changes in neuronal activity and extracellular concentrations of ions were measured in rat striatum for 60-90 min after intrastriatal injection of quinolinic acid, an agonist of the N-methyl-D-aspartate receptor. The excitotoxin induced bursts of synchronous electrical activity which were accompanied by rises in [K+]e (to approximately 6 mM) and decreases in [Ca2+]e (by less than 0.1 mM); [H+]e usually increased (0.1-0.3 pH unit) after a short and small (< 0.1 pH unit) alkaline shift. The magnitude and frequency of these periodic changes decreased with time; after 90 min the amplitudes fell to 10-20% of the early values and the frequency to about one every 8 min as compared to one every 2-3 min immediately after quinolinate injection. By 90 min there was an increase in [K+]e from 3.3 mM to 4.2 mM and a decrease in [Ca2+]e from 1.34 mM to 1.30 mM. It is postulated that activation of the N-methyl-D-aspartate receptor causes disturbances in neuronal activity and ion gradients; restoration of the original ionic balances raises utilization of ATP and places an additional demand on energy-producing pathways. Increased influx of calcium into neurons may lead to an enhanced accumulation and subsequent overload of mitochondria with the cation. This, in turn, could result in dysfunction of the organelles and account for the decrease in respiration and [ATP]/[ADP] that have been observed previously in this model. The results of the present study lead to the conclusion that quinolinic acid produces early changes in activity of striatal neurons and movements of several cations which may contribute to subsequent abnormalities in energy metabolism and ultimately, cell death.