RT Journal Article SR Electronic T1 Depolarization-induced neurite outgrowth in PC12 cells requires permissive, low level NGF receptor stimulation and activation of calcium/calmodulin-dependent protein kinase JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 5966 OP 5975 DO 10.1523/JNEUROSCI.15-09-05966.1995 VO 15 IS 9 A1 M Solem A1 T McMahon A1 RO Messing YR 1995 UL http://www.jneurosci.org/content/15/9/5966.abstract AB Neuronal activity is required for normal neural development. Excessive activity can cause abnormal growth of neural processes and may contribute to formation of epileptic foci. Using PC12 cells, we investigated mechanisms by which depolarization regulates neurite growth. Depolarization with 45 mM KCl induced neurite outgrowth only if NGF receptors were partly activated by overexpression of p140trkA or by treatment with a low concentration of NGF that alone was insufficient to stimulate neurite formation. Depolarization-induced neurite growth was reduced by inhibitors of L-type Ca2+ channels, Ca2+/calmodulin- dependent protein (CaM) kinases II and IV, and transcription. These results identify a novel mechanism by which depolarizing stimuli synergize with subthreshold activation of NGF receptors to induce neurite growth through a Ca2+ and CaM kinase-dependent signal transduction pathway.