Neuronal growth factor regulation of two different sodium channel types through distinct signal transduction pathways

Neuronal growth factors regulate the expression of voltage-activated sodium current in differentiating sympathetic neurons and PC12 cells. We show that, in PC12 cells, the NGF- and FGF-induced sodium current results from increased expression of two distinct sodium channel types. Sodium current results from the rapid induction of a novel sodium channel transcript, also found in peripheral neurons, and from the long term induction of brain type II/IIA mRNA. Expression of the type II/IIA sodium channel requires activation of the cyclic AMP-dependent protein kinase (A-kinase), whereas induction of the peripheral neuron type sodium channel occurs through an A-kinase-independent signal transduction pathway. These findings suggest that the two sodium channel types act in concert to ensure the generation of action potentials during neuronal differentiation.