Hippocampal interneurons and pyramidal cells differ in their sensitivity to ischaemia and excitotoxic neurodegeneration, with interneurones being markedly less sensitive to these insults (Lipton, 1999). This may reflect differences in Ca²⁺ handling or receptor expression/subunit composition between these cell types. To investigate whether differences in NMDA receptor function could be involved in this phenomenon, we compared electrophysiological and Ca²⁺ responses to NMDA application in pyramidal cells and interneurones in the CA1 hippocampal region.

Hippocampal slices were obtained from 14- to 19-day-old rats, killed humanely by cervical dislocation. Whole-cell patch clamp recording, using a potassium gluconate-based intracellular solution, was combined with ratiometric Ca²⁺ imaging by including the Ca²⁺-sensitive dye bis-fura 2 (150 µM) in the pipette solution. Somatic Ca²⁺ measurements were made using a conventional imaging system (Universal Imaging), with changes in intracellular Ca²⁺ levels expressed as changes in fluorescence ratio units (r.u.). Cell types were identified by their location (pyramidal layer or stratum oriens) and electrophysiological properties. Responses to bath application of NMDA (3-5 min, 10 µM; in the presence of 0.5 µM TTX) were investigated at -60 and -30 mV in both interneurones and pyramidal cells. Data are expressed as means ± S.E.M. and one-way ANOVA was used as the statistical test.

NMDA responses across pyramidal cells were similar and exhibited strong voltage dependence both in the evoked inward current and calcium rise. In pyramidal neurons at -60 mV NMDA induced an inward current of 94.0 ± 18.2 pA (n = 5), with a range of 68 to 160 pA. However, this current was associated with no detectable increase in somatic Ca²⁺ levels. When NMDA was applied at -30 mV, it induced a current of 859.0 ± 92.7 pA (7.7 ± 1.1-fold increase) associated with a mean Ca²⁺ rise of 0.77 ± 0.06 r.u. In contrast to pyramidal cells, NMDA responses in interneurones were more heterogeneous, with the inward current varying from 19 to 520 pA at -60 mV (mean 120 ± 55 pA; n = 9) and in two cells NMDA application was associated with a small Ca²⁺ rise of 0.05 and 0.17 r.u. The NMDA responses at -30 mV were significantly smaller compared to pyramidal cells (P < 0.01). The mean inward current was 254.8 ± 116.6 pA (2.1 ± 0.6-fold increase), associated with a mean Ca²⁺ rise of 0.29 ± 0.1 r.u.

These data show that interneurones and pyramidal cells respond differently to NMDA application with distinct voltage dependence, resulting in enhanced NMDA-evoked Ca²⁺ signals in pyramidal cells. Such properties could underlie their differing sensitivity to toxic insults.

This work was supported by the BBSRC and EU (Marie Curie).