Quinolinate activation of N-methyl-D-aspartate ion channels in rat hippocampal neurons

The cell attached configuration of the patch clamp method has been used to determine the single channel properties of the ion channel coupled to activation of the N-methyl-D-aspartate (NMDA) receptor by the endogenous NMDA agonist quinolinate. Openings of the NMDA channel were recorded from cultured CA1 hippocampal neurons over a hyperpolarizing potential range from cell resting potential. The slope conductance of the channel was 39 pS with 75 microM quinolinate, 1.8 mM Ca2+ and no Mg2+ in the patch pipette. The mean channel open times were decreased with hyperpolarization in an exponential manner with a mean slope of 0.6 ms/20 mV. Addition of Mg2+ to the pipette (at 30 microM) caused the mean open time, at a potential of -100 mV, to be decreased to a value about one-third that of control. The mean open times with quinolinate as the agonist were shorter for all potentials studied compared with activation of the NMDA receptor with NMDA or D-cis-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD). Both the mean open times and the channel amplitudes were significantly altered when the bath temperature was decreased; the Q10 values for both quantities were in excess of 2.8.