Neurotrophin regulation of sodium and calcium channels in human neuroblastoma cells

URBANO FJ ; BUÑO W

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: New York, USA.; Año: 2000 vol. 96 p. 439 - 443

0306-4522

Neurotrophins, acting through tyrosine kinase family genes, are essential for neuronal differentiation. The expression of tyrosine kinase family genes is prognostic in neuroblastoma, and neurotrophins reduce proliferation and induce differentiation, indicating that neuroblastoma are regulated by neurotrophins. We tested the effects of nerve growth factor and brain-derived neurotrophic factor on Na and Ca currents, using the whole-cell patch-clamp technique, in human neuroblastoma NB69 cells. Control cells exhibited a slow tetrodotoxin-resistant (IC50 98 nM) Na current and a high-voltage-activated Ca current. Exposure to nerve growth factor (50 ng/ml) and/or brain-derived neurotrophic factor (5 ng/ml) produced the expression of a fast tetrodotoxin-sensitive (IC50 10 nM) Na current after day 3, and suppressed the slow tetrodotoxin-resistant variety. The same type of high-voltage-activated Ca current was expressed in control and treated cells. The treatment increased the surface density of both Na and Ca currents with time after plating, from 17 pA/pF at days 3?5 and 1?5 to 34 and 30 pA/pF, after days 6?10, respectively. Therefore, both nerve growth factor and brain-derived neurotrophic factor, acting through different receptors of the tyrosine kinase family and also possibly the tumor necrosis factor receptor-II, were able to regulate differentiation and the expression of Na and Ca channels, partially reproducing the modifications induced by diffusible astroglial factors. We show that neurotrophins induced differentiation to a neuronal phenotype and modified the expression of Na and Ca currents, partially reproducing the effects of diffusible astroglial factors.