Nerve growth factor acts through cAMP-dependent protein kinase to increase the number of sodium channels in PC12 cells.
cAMP-dependent protein kinase (PKA) and phospholipid-dependent protein kinase (PKC) play a role in nerve growth factor (NGF)-mediated differentiation. In PC12 cells, NGF causes neurite outgrowth and increases the number of voltage-gated Na+ channels. Neurite outgrowth involves in part activation of PKC. How NGF regulates Na+ channel number is unknown. Using patch-clamp techniques, we find that agents activating PKC, including phorbol esters and a ras oncogene product (p21) that induces neurites, caused little increase in channel number. In contrast, agents increasing intracellular cAMP were as effective as NGF. A specific protein inhibitor of the PKA catalytic subunit blocked increases by NGF or cAMP. Thus, NGF increases Na+ channel number in PC12 cells in part by activating PKA but apparently not PKC.
Kalman
D
D
Department of Biology, University of California, Los Angeles 90024.
Wong
B
B
Horvai
A E
AE
Cline
M J
MJ
O'Lague
P H
PH
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000310:Adrenal Gland Neoplasms; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D003563:Cyclic CMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D011905:Genes, ras; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010673:Pheochromocytoma; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D009414:Nerve Growth Factors; D015222:Sodium Channels; D005576:Colforsin; D003995:Dibutyryl Cyclic GMP; D003563:Cyclic CMP; D013779:Tetrodotoxin; D003994:Bucladesine; C053441:dibutyryl cyclic-3',5'-cytidine monophosphate; D011494:Protein Kinases; D015056:1-Methyl-3-isobutylxanthine; D004121:Dimethyl Sulfoxide