The activity of cAMP-dependent protein kinase is required at a posttranslational level for induction of voltage-dependent sodium channels by peptide growth factors in PC12 cells

David D. Ginty, Gary R. Fanger, John A. Wagner, Robert A. Maue

Research output: Contribution to journalArticle

Abstract

The synthesis and expression of voltage-dependent sodium (Na) channels is a crucial aspect of neuronal differentiation because of the central role these ion channels play in the generation of action potentials and the transfer of information in the nervous system. We have used rat pheochromocytoma (PC12) cell lines deficient in cAMP-dependent protein kinase (PKA) activity to examine the role of PKA in the induction of Na channel expression by nerve growth factor (NGF) and basic FGF (bFGF). In the parental PC12 cell line both NGF and bFGF elicit an increase in the density of functional Na channels, as determined from whole-cell patch clamp recordings. This increase does not occur in two PC12 cell lines deficient in both isozymes of PKA (PKAI and PKAII), and is strongly reduced in a third line deficient in PKAII, but not PKAI. Despite the inability of the neurotrophic factors to induce functional Na channel expression in the PKA-deficient cells, Northern blot hybridization studies and saxitoxin binding assays of intact cells indicate that NGF and bFGF are still capable of eliciting increases in both Na channel mRNA and Na channel protein in the membrane. Thus, PKA activity appears to be necessary at a posttranslational step in the synthesis and expression of functional Na channels, and thereby plays an important role in determining neuronal excitability.

Original languageEnglish (US)
Pages (from-to)1465-1473
Number of pages9
JournalJournal of Cell Biology
Volume116
Issue number6
StatePublished - Mar 1992
Externally publishedYes

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Sodium Channels
PC12 Cells
Cyclic AMP-Dependent Protein Kinases
Protein Kinases
Intercellular Signaling Peptides and Proteins
Nerve Growth Factor
Peptides
Saxitoxin
Cell Line
Nerve Growth Factors
Ion Channels
Northern Blotting
Nervous System
Isoenzymes
Action Potentials
Membrane Proteins
Messenger RNA

ASJC Scopus subject areas

  • Cell Biology

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The activity of cAMP-dependent protein kinase is required at a posttranslational level for induction of voltage-dependent sodium channels by peptide growth factors in PC12 cells. / Ginty, David D.; Fanger, Gary R.; Wagner, John A.; Maue, Robert A.

In: Journal of Cell Biology, Vol. 116, No. 6, 03.1992, p. 1465-1473.

Research output: Contribution to journalArticle

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