Electrophysiological analysis of NMDA receptor subunit changes in the aging mouse cortex

NMDA receptors play an important role in memory processes and plasticity in the brain. We have previously demonstrated a significant decrease in NMDAR epsilon 2 subunit mRNA and protein with increasing age in the C57Bl/6 mous e frontal cortex. In the present study, two-electrode voltage clamp electro physiology on Xenopus oocytes injected with total RNA harvested from the fr ontal cortex of young and old C57Bl mice was used to detect changes in rece ptor composition during aging. Ifenprodil concentration-response curves, ma gnesium current-voltage curves, and single channel conductances were determ ined for native receptors. In addition, ifenprodil and magnesium curves wer e generated for recombinant NMDA receptors of varying subunit ratios. Ifenp rodil dose-response curves for all receptors were biphasic. The low affinit y component of the curve increased slightly with age, while the high affini ty population decreased, mimicking recombinant receptors with decreasing le vels of epsilon 2. A decrease in maximal current was also observed in aged animals with decreased levels of epsilon 2, although single channel conduct ances were identical between young and old mice. In addition. an increase i n sensitivity to magnesium was observed for receptors from older animals. R esults are consistent with the interpretation that the epsilon 2 subunit is reduced in older mouse frontal cortex. A change in NMDA receptor subunit c omposition could influence memory processes during aging. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.