Journal of Neurophysiology, Vol 72, Issue 4 1538-1548, Copyright © 1994 by APS

ARTICLES

Blockade of NMDA-activated channels by magnesium in the immature rat hippocampus

G. J. Strecker, M. B. Jackson and F. E. Dudek
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523.

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 Mg(2+)-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 Mg(2+)-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 Mg(2+)-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 Mg(2+)-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.

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