Single channel properties of the N-methyl-D-aspartate receptor channel using NMDA and NMDA agonists: on-cell...

The cell-attached patch-clamp mode has been applied in cultured rat hippocampal neurons to record single channel currents through the ion channel which is coupled to activation of the N-methyl-D-aspartate (NMDA) receptor. A channel, with a conductance of 37 pS, was studied with either NMDA or D-cis-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) in the patch pipette. The mean open time of the channels with NMDA in the pipette was near 5 ms at -80 mV and was diminished about 0.7 ms for each 20 mV of hyperpolarization. The mean open times with ACPD in the pipette were longer at all voltages studied and for both agonists the mean open times showed an exponential dependence on patch potential. Distributions for the channel open times were generally well-fit with single exponentials, whereas distributions for closed times required two-component fits. In some instances, the open distributions also showed a second, rapid time component. When Mg2+ was included in the pipette (40 or 100 microM), the mean open times were significantly diminished with the effect increasing with the magnitude of the hyperpolarization. Both the amplitudes and mean open times of the NMDA channel were strongly modulated by temperature with Q10 values in excess of 2.5.