Memantine protects hippocampal neuronal function in murine human immunodeficiency virus type 1 encephalitis.
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.