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NRSF Causes cAMP-Sensitive Suppression of Sodium Current in Cultured Hippocampal Neurons

NRSF Causes cAMP-Sensitive Suppression of Sodium Current in Cultured Hippocampal Neurons Abstract The 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. Footnotes Address for reprint requests: H. Nadeau, JPL M/S 183-301, 4800 Oak Grove Dr., Pasadena, CA, 91109 (E-mail: nadeau@mail2.jpl.nasa.gov ). Copyright © 2002 The American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurophysiology The American Physiological Society

NRSF Causes cAMP-Sensitive Suppression of Sodium Current in Cultured Hippocampal Neurons

Nadeau, H.; Lester, H. A.
Journal of Neurophysiology , Volume 88 (1): 409 – Jul 1, 2002
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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0022-3077
eISSN
1522-1598
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Abstract

Abstract The 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. Footnotes Address for reprint requests: H. Nadeau, JPL M/S 183-301, 4800 Oak Grove Dr., Pasadena, CA, 91109 (E-mail: nadeau@mail2.jpl.nasa.gov ). Copyright © 2002 The American Physiological Society

Journal

Journal of Neurophysiology – The American Physiological Society

Published: Jul 1, 2002

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