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

Eilon D. Kirson, Claudia Schirra, Arthur Konnerth, Yoel Yaari*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

1. Whole-cell patch-clamp recordings of iontophoretically induced N-methyl-D-aspartate (NMDA) receptor-mediated currents (I(NMDA)) in CA1 pyramidal cells in hippocampal slices from 1- to 40-day-old rats were used to characterize developmental changes in the Mg2+ sensitivity of NMDA receptors. 2. The dose-response relations for extracellular Mg2+ blockade of I(NMDA) indicated a high affinity binding of Mg2+ to NMDA receptors at membrane potentials more negative than -60 mV, independent of postnatal age. 3. Depolarizing the cells unblocked NMDA receptors by decreasing their affinity 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 pyramidal cells of all ages. The sensitivity of I(NMDA) to ifenprodil was greatest during the first postnatal week and decreased thereafter, indicating an enhanced contribution of NR2B subunit-containing NMDA receptors to I(NMDA) in the first week after birth. 5. In the first postnatal week, the ifenprodil-insensitive I(NMDA) component had a lower voltage dependence than the total I(NMDA). In older pyramidal cells, 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 concomitant developmental changes in NMDA subunit mRNA expression. The mRNA for the NR2D subunit was detected during the first postnatal week in 50% of the cells and disappeared thereafter. The proportion of cells expressing the NR2A and NR2B subunits remained relatively constant throughout the first five postnatal weeks. 7. We conclude that NMDA receptors in hippocampal CA1 pyramidal cells are effectively 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 downregulation of NR2D subunit expression in developing CA1 pyramidal cells.

Original languageEnglish
Pages (from-to)99-111
Number of pages13
JournalJournal of Physiology
Volume521
Issue number1
DOIs
StatePublished - 15 Nov 1999
Externally publishedYes

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