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

Nadeau, H. and Lester, H. A. (2002) NRSF Causes cAMP-Sensitive Suppression of Sodium Current in Cultured Hippocampal Neurons. Journal of Neurophysiology, 88 (1). pp. 409-421. ISSN 0022-3077. doi:10.1152/jn.2002.88.1.409.

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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.

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Lester, H. A.0000-0002-5470-5255
Additional Information:© 2002 The American Physiological Society. Received 20 December 2001; accepted in final form 7 March 2002. We thank D. J. Anderson for useful suggestions and discussions and A. J. Paquette for critically reading the manuscript. This work was supported by Burroughs-Wellcome and National Institute of Mental Health Grant MH-490176. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Burroughs Wellcome FundUNSPECIFIED
Issue or Number:1
Record Number:CaltechAUTHORS:20200612-113333802
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Official Citation:NRSF Causes cAMP-Sensitive Suppression of Sodium Current in Cultured Hippocampal Neurons H. Nadeau and H. A. Lester Journal of Neurophysiology 2002 88:1, 409-421
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103869
Deposited By: George Porter
Deposited On:12 Jun 2020 19:25
Last Modified:16 Nov 2021 18:26

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