Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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Adrenal Gland Neoplasms
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Animals
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Bucladesine / pharmacology
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Cell Differentiation / drug effects
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Cell Line
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Colforsin / pharmacology
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Cyclic CMP / analogs & derivatives
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Cyclic CMP / pharmacology
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Dibutyryl Cyclic GMP / pharmacology
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Dimethyl Sulfoxide / pharmacology
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Electric Conductivity
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Electrophysiology / methods
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Gene Expression / drug effects
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Genes, ras
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Kinetics
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Nerve Growth Factors / pharmacology*
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Pheochromocytoma
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Protein Kinases / metabolism*
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Rats
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Sodium Channels / drug effects
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Sodium Channels / physiology*
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Tetrodotoxin / pharmacology
Substances
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Nerve Growth Factors
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Sodium Channels
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Colforsin
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Dibutyryl Cyclic GMP
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Cyclic CMP
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Tetrodotoxin
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Bucladesine
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dibutyryl cyclic-3',5'-cytidine monophosphate
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Protein Kinases
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1-Methyl-3-isobutylxanthine
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Dimethyl Sulfoxide