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Journal of Neuroscience, Vol 10, 2626-2637, Copyright © 1990 by Society for Neuroscience
Differential effects of NGF, FGF, EGF, cAMP, and dexamethasone on neurite outgrowth and sodium channel expression in PC12 cells
JD Pollock, M Krempin and B Rudy
Division of Biology, California Institute of Technology, Pasadena 91125.
PC12 cells are a pheochromocytoma cell line that can be made to
differentiate into sympatheticlike neurons by nerve growth factor (NGF). An
essential component of the NGF-induced differentiation is the development
of action potentials and sodium channels. Using whole-cell clamp we have
confirmed that NGF produces a 5- to 6-fold increase in sodium channel
density. The sodium channels induced by NGF are not different from those in
cells not treated with NGF and are similar to those in other cell types.
Basic fibroblast growth factor (FGF), another growth factor that causes
PC12 cells to differentiate into sympathetic-like neurons, also produces a
5- to 6-fold increase in sodium current density with channels
indistinguishable from those in PC12 cells treated and not treated with
NGF. Basic FGF produces the same or somewhat larger increase in sodium
channel density but much less neurite outgrowth. In contrast, epidermal
growth factor does not produce neurite outgrowth but induces a small,
reproducible increase in sodium channel density. Cyclic AMP produces
spike-like processes but not neurites and results in a decrease in sodium
current and sodium current density. Dexamethasone, a synthetic
glucocorticoid, inhibits the increase in sodium current and sodium current
density but does not antagonize the neurite outgrowth induced by NGF. Thus,
although the increase in sodium channel expression induced by NGF and basic
FGF parallels the changes in morphology that lead to neurite outgrowth, it
clearly does not depend on them. The results show that different aspects of
neuronal differentiation might be independently regulated by the
microenvironment.
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