A Potential Excitability Was Induced by Basic Fibroblast Growth Factor during Early Differentiation of Neurons from Mouse Embryonic Stem Cells in vitro.

We report that basic fibroblast growth factor (bFGF) induces the release of glutamate in ES-derived neurons during early stages of differentiation. Changes of Ca2+concentration labeled by fluorescence intensity occurred in response to minimal concentrations of glutamate. The Ca2+concentration was changed more rapidly by bFGF than by glutamate during the early stages of differentiation of ES-derived neurons. High concentrations of the inhibitor MK801, a N-methyl-D-aspartate (NMDA) receptor antagonist applied before bFGF stimulation caused a dramatic decrease of fluorescence intensity in neurons derived from both hippocampal and ES cells. These results showed that bFGF induces glutamate release and an increase of [Ca2+] in neurons during early stages of differentiation, and that the increase of [Ca2+] can be inhibited by MK801. Therefore, we concluded that bFGF serves not only as a neurotrophin but also as a stimulator of excitability during the differentiation of ES cells into neurons.