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.
D'Arcangelo
G
G
Department of Neurobiology and Behavior, State University of New York, Stony Brook 11794-5230.
Paradiso
K
K
Shepherd
D
D
Brehm
P
P
Halegoua
S
S
Mandel
G
G
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D015870:Gene Expression; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009414:Nerve Growth Factors / Q000502:physiology*; D016716:PC12 Cells; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D012964:Sodium / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D015222:Sodium Channels; D005346:Fibroblast Growth Factors; D012964:Sodium; D000242:Cyclic AMP; D011494:Protein Kinases