Neurotrophins differentially regulate voltage-gated ion channels.

Neurotrophic factors profoundly affect neuronal differentiation, but whether they influence neuronal phenotype in instructive ways remains unclear: do different neurotrophic factors always trigger identical programs of differentiation or can each impose distinct functional properties even when acting upon the same population of target neurons? We addressed this issue by examining the regulatory effects of the four neurotrophins on the molecular components of electrical excitability, voltage-gated ion channels, within a single cellular context. Using patch clamp methods, we studied neurotrophin regulation of voltage-gated sodium, calcium, and potassium currents in SK-N-SH neuroblastoma cells. We found that each neurotrophin induced a unique pattern of expression of ionic currents despite similar activation of initial signal transduction events. Thus, each neurotrophin imposed a different excitable phenotype even when acting upon the same target cells.