Selective induction of brain type II Na+ channels by nerve growth factor

Gail Mandel, S. S. Cooperman, R. A. Maue, Richard Goodman, Paul Brehm

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116 Citations (Scopus)

Abstract

Cells derived from a rat pheochromocytoma (PC12 cells) can generate an action potential only upon treatment with nerve growth factor. Using electrophysiological methods, we found that the appearance of action potentials in nerve growth factor-treated PC12 cells can be explained by an increase in the density of Na+ channels. The functional properties of Na+ channels in PC12 cells are similar to those described for peripheral nerves but appear to be different from Na+ channels synthesized in Xenopus oocytes injected with brain type II Na+-channel mRNA. To determine if PC12 cells express the brain type II Na+-channel gene, we performed RNase-protection analyses using probes than can distinguish between the brain type I and type II Na+-channel mRNAs. The results from these studies indicate that undifferentiated PC12 cells express the type II but not the type I Na+-channel gene. Treatment with nerve growth factor increases expression of the type II Na+-channel gene but has no effect on type I gene expression. Our findings suggest that Na+-channel excitability in PC12 cells is due to the specific induction of the brain type II gene by nerve growth factor.

Original languageEnglish (US)
Pages (from-to)924-928
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number3
StatePublished - 1988
Externally publishedYes

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PC12 Cells
Nerve Growth Factor
Brain
Genes
Action Potentials
Messenger RNA
Pheochromocytoma
Ribonucleases
Xenopus
Peripheral Nerves
Oocytes
Gene Expression

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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AU - Mandel, Gail

AU - Cooperman, S. S.

AU - Maue, R. A.

AU - Goodman, Richard

AU - Brehm, Paul

PY - 1988

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N2 - Cells derived from a rat pheochromocytoma (PC12 cells) can generate an action potential only upon treatment with nerve growth factor. Using electrophysiological methods, we found that the appearance of action potentials in nerve growth factor-treated PC12 cells can be explained by an increase in the density of Na+ channels. The functional properties of Na+ channels in PC12 cells are similar to those described for peripheral nerves but appear to be different from Na+ channels synthesized in Xenopus oocytes injected with brain type II Na+-channel mRNA. To determine if PC12 cells express the brain type II Na+-channel gene, we performed RNase-protection analyses using probes than can distinguish between the brain type I and type II Na+-channel mRNAs. The results from these studies indicate that undifferentiated PC12 cells express the type II but not the type I Na+-channel gene. Treatment with nerve growth factor increases expression of the type II Na+-channel gene but has no effect on type I gene expression. Our findings suggest that Na+-channel excitability in PC12 cells is due to the specific induction of the brain type II gene by nerve growth factor.

AB - Cells derived from a rat pheochromocytoma (PC12 cells) can generate an action potential only upon treatment with nerve growth factor. Using electrophysiological methods, we found that the appearance of action potentials in nerve growth factor-treated PC12 cells can be explained by an increase in the density of Na+ channels. The functional properties of Na+ channels in PC12 cells are similar to those described for peripheral nerves but appear to be different from Na+ channels synthesized in Xenopus oocytes injected with brain type II Na+-channel mRNA. To determine if PC12 cells express the brain type II Na+-channel gene, we performed RNase-protection analyses using probes than can distinguish between the brain type I and type II Na+-channel mRNAs. The results from these studies indicate that undifferentiated PC12 cells express the type II but not the type I Na+-channel gene. Treatment with nerve growth factor increases expression of the type II Na+-channel gene but has no effect on type I gene expression. Our findings suggest that Na+-channel excitability in PC12 cells is due to the specific induction of the brain type II gene by nerve growth factor.

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