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NRSF causes cAMP-sensitive suppression of sodium current in cultured hippocampal neuronsThe neuron restrictive silencer factor (NRSF/REST) has been shown to bind to the promoters of many neuron-specific genes and is able to suppress transcription of Na(+) channels in PC12 cells, although its functional effect in terminally differentiated neurons is unknown. We constructed lentiviral vectors to express NRSF as a bicistronic message with green fluorescent protein (GFP) and followed infected hippocampal neurons in culture over a period of 1-2 wk. NRSF-expressing neurons showed a time-dependent suppression of Na(+) channel function as measured by whole cell electrophysiology. Suppression was reversed or prevented by the addition of membrane-permeable cAMP analogues and enhanced by cAMP antagonists but not affected by increasing protein expression with a viral enhancer. Secondary effects, including altered sensitivity to glutamate and GABA and reduced outward K(+) currents, were duplicated by culturing GFP-infected control neurons in TTX. The striking similarity of the phenotypes makes NRSF potentially useful as a genetic "silencer" and also suggests avenues of further exploration that may elucidate the transcription factor's in vivo role in neuronal plasticity.
Document ID
20040088243
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Nadeau, H.
(California Institute of Technology Pasadena, California 91125, United States)
Lester, H. A.
Date Acquired
August 21, 2013
Publication Date
July 1, 2002
Publication Information
Publication: Journal of neurophysiology
Volume: 88
Issue: 1
ISSN: 0022-3077
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: MH-490176
Distribution Limits
Public
Copyright
Other

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