Early postnatal switch in magnesium sensitivity of NMDA receptors in rat CA1 pyramidal cells

1. Whole-cell patch-damp recordings of iontophoretically induced N-methyl-D -aspartate (NMDA) receptor-mediated currents (I-NMDA) in CA1 pyramidal cell s in hippocampal slices from 1- to 40-day-old rats were used to characteriz e developmental changes in the Mg2+ sensitivity of NMDA receptors. 2. The dose-response relations for extracellular Mg2+ blockade of I-NMDA in dicated a high affinity binding of Mg2+ to NMDA receptors at membrane poten tials more negative than -60 mV, independent of postnatal age. 3. Depolarizing the cells unblocked NMDA receptors by decreasing their affi nity for Mg2+. The efficacy of depolarization in unblocking NMDA receptors markedly increased after postnatal day 4 (P4), endowing the receptors with a greater voltage dependence. 4. The NR2B subunit-specific NMDA antagonist ifenprodil reduced I-NMDA in p yramidal cells of all ages. The sensitivity of I-NMDA to ifenprodil was gre atest during the first postnatal week and decreased thereafter, indicating an enhanced contribution of NR2B subunit-containing NMDA receptors to I-NMD A in the first week after birth. 5. In the first postnatal week, the ifenprodil-insensitive INMDA component had a lower voltage dependence than the total I-NMDA. In older pyramidal ce lls, the voltage dependence of the ifenprodil-insensitive component and the total I-NMDA were similar. 6. In another set of CA1 pyramidal cells, single-cell reverse transcription and polymerase chain reaction (RT-PCR) were used to characterize concomita nt developmental changes in NMDA subunit mRNA expression. The mRNA for the NR2D subunit was detected during the first postnatal week in 50% of the cel ls and disappeared thereafter. The proportion of cells expressing the NR2A and NR2B subunits remained relatively constant throughout the first five po stnatal weeks. 7. We conclude that NMDA receptors in hippocampal CA1 pyramidal cells are e ffectively blocked by Mg2+ at all ages. After 4 days they become much less sensitive to Mg2+ at depolarized membrane potentials. This postnatal switch in voltage control of Mg2+ binding to NMDA receptors may be due to the dow nregulation of NR2D subunit expression in developing CA1 pyramidal cells.