Ion channels activated by quinolinic acid in cultured rat hippocampal neurons

The membrane responses to quinolinic acid, an excitotoxic brain metabolite, were studied in cultured rat hippocampal neurons with the patch-clamp technique. In the whole-cell recording mode, pressure applications of quinolinic acid elicited inwardly directed membrane currents over a membrane potential range of -60 to -5 mV. The current response reversed at about 0 mV. The current-voltage (I-V) relation of the response had a negative slope conductance at membrane potentials more negative than -40 mV. On removal of Mg2+ from the extracellular solution, the current response showed no region of negative slope conductance at potentials more positive than -60 mV. In Mg2+-free solution applications of quinolinic acid elicited discrete pulse-like current flows through the outside-out membrane patch. The single channel conductance was 40-46 pS over a membrane potential range of -40 to -80 mV, and 50-55 pS at membrane potentials more positive than +30 mV, showing an outward rectification. These values of the single channel conductance were similar to those of the main conducting state of the channels activated by N-methyl-D-aspartate (NMDA). The responses to quinolinic acid were completely suppressed by the NMDA receptor antagonist (+/-)-2-amino-5-phosphonovaleric acid. The results indicate that quinolinic acid selectively activates NMDA receptors in the cultured rat hippocampal neurons.