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

Abstract

Changes in neuronal activity and extracellular concentrations of ions were measured in rat striatum for 60–90min 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 6mM) and decreases in [Ca2+]e (by less than 0.1mM); [H+]e usually increased (0.1–0.3pH unit) after a short and small (<0.1pH unit) alkaline shift. The magnitude and frequency of these periodic changes decreased with time; after 90min the amplitudes fell to 10–20% of the early values and the frequency to about one every 8min as compared to one every 2–3min immediately after quinolinate injection. By 90min there was an increase in [K+]e from 3.3mM to 4.2mM and a decrease in [Ca2+]e from 1.34mM to 1.30mM. 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.