BLOCKADE OF NMDA-ACTIVATED CHANNELS BY MAGNESIUM IN THE IMMATURE RAT HIPPOCAMPUS

1. N-methyl-D-aspartate (NMDA)-receptor single-channel currents were examined in outside-out patches from thin slices of rat hippocampus to examine possible age dependence in the Mg2+-block of NMDA-mediated responses. The kinetics of Mg2+ block, among other channel properties, were compared between CA1 pyramidal cells from neonatal and 2-wk-old animals and dentate gyrus granule cells from neonatal and 4-wk-old animals. 2. Two distinct conductance states were seen consistently in nominally Mg2+-free solutions. The main conductance state was 50 and 56 pS in pyramidal cells and granule cells, respectively. The difference in NMDA-receptor channel conductance between the two cell types was statistically significant at all ages examined. Both cell types exhibited a less frequent 35- to 40-pS conductance state. 3. Channel closing rates showed no intrinsic voltage dependence in Mg2+-free solutions in any group. Open times became strongly voltage dependent when Mg2+ was added. The rate of block by Mg2+ was similar in all groups. 4. Voltage and Mg2+ influenced primarily the shortest time constant of shut-time distributions. Longer components varied relatively little with voltage or [Mg2+]. The effects of voltage and [Mg2+] suggest that brief shuttings represent closed states in the absence of Mg2+ and primarily a Mg2+-blocked state in the presence of Mg2+. 5. The rate of unblocking by Mg2+ was similar in all groups. Thus the dissociation constant for Mg2+ binding (i.e., the ratio of the unblocking and blocking rates) also showed little variation. 6. NMDA-receptor channels in two regions of the hippocampus behaved in a qualitatively similar fashion both in neonates and 2-or 4-wk-old rats. These observations are inconsistent with previous studies obtained using other methods, which suggested that block of NMDA receptor channels by Mg2+ increases substantially with age. Nevertheless, subtle developmental and regional differences in other aspects of NMDA-receptor channel behavior were detected, perhaps reflecting variations in molecular structure tailored to specific functional requirements.