Modulation of N-methyl-D-aspartic acid receptors by extracellular calcium in immature and adult hippocampal slices: whole cell recordings in CA3 pyramidal cells.

Lowering extracellular calcium concentration [Ca2+]o in rat hippocampal slices can lead to an induction of epileptiform activity. It has been shown that this effect is more pronounced in slices of neonatal rats (postnatal day, PND 8-19) than in mature slices (> PND 40) and it has been suggested that unique N-methyl-D-aspartic acid (NMDA) receptor properties of immature rat hippocampal pyramidal cells contribute to this developmental effect. In a voltage clamp experiment we tested NMDA receptor properties in hippocampal pyramidal cells by measuring NMDA receptor mediated currents evoked by iontophoretic applied NMDA in the basal dendrites of CA3 pyramidal neurons. We found that lowering extracellular calcium from 2 to 1 mM, increases NMDA evoked inward current in pyramidal cells around the resting membrane potential. However, this effect is observed in slices of neonatal as well as in slices of mature rats, suggesting that there is no difference in NMDA receptor sensitivity to extracellular Ca2+ between these two age groups. The modulation of the NMDA receptor by extracellular calcium at physiological concentrations can have important consequences in pathological conditions during which extracellular calcium reaches low levels. Because this 'hypocalcemic' condition induces a larger current influx via the NMDA receptor channel at resting membrane potentials, it can further enhance cellular excitability and contribute to sustain epileptiform activity.