Epidermal growth factor selectively enhances NMDA receptor-mediated increase of intracellular Ca2+ concentration in rat hippocampal neurons.

We have previously reported that recombinant human epidermal growth factor (hEGF) facilitates induction of hippocampal long-term potentiation (LTP). In order to clarify the mechanism underlying the LTP-facilitating effect of hEGF, the influence of hEGF on intracellular Ca2+ concentration ([Ca2+]i) of hippocampal neurons was investigated using dissociated cell cultures. Changes in [Ca2+]i were measured by microfluorometrically monitoring the fluorescence intensities from individual neurons loaded with fura-2. Application of hEGF (0.6-20 ng/ml) alone did not affect the basal level of [Ca2+]i in cultured hippocampal neurons, but significantly enhanced the [Ca2+]i increase induced by L-glutamate (3 x 10(-6) M). The N-methyl-D-aspartate (NMDA) (10(-5) and 3 x 10(-5) M)-induced [Ca2+]i increase was also enhanced by hEGF, but the quisqualate (10(-7) and 3 x 10(-7) M)-induced response was not affected by the presence of hEGF. These results suggest that hEGF selectively enhances the NMDA receptor-mediated responses in hippocampal neurons. This action of hEGF may underlie the facilitation of hippocampal LTP.