Get access

Modulation of the voltage-gated sodium current in rat striatal neurons by DARPP-32, an inhibitor of protein phosphatase

Authors

  • Schiffmann,

    1. 1 Brain Research Unit, Université Libre de Bruxelles, Brussels, Belgium, 21Collège de France, Chaire de Neuropharmacologie, INSERM U114, Paris, France, 32Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY, USA, 43Institut A. Fessard, CNRS, Gif-sur-Yvette, France
    Search for more papers by this author
  • Desdouits,

    1. 1 Brain Research Unit, Université Libre de Bruxelles, Brussels, Belgium, 21Collège de France, Chaire de Neuropharmacologie, INSERM U114, Paris, France, 32Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY, USA, 43Institut A. Fessard, CNRS, Gif-sur-Yvette, France
    Search for more papers by this author
  • Menu,

    1. 1 Brain Research Unit, Université Libre de Bruxelles, Brussels, Belgium, 21Collège de France, Chaire de Neuropharmacologie, INSERM U114, Paris, France, 32Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY, USA, 43Institut A. Fessard, CNRS, Gif-sur-Yvette, France
    Search for more papers by this author
  • Greengard,

    1. 1 Brain Research Unit, Université Libre de Bruxelles, Brussels, Belgium, 21Collège de France, Chaire de Neuropharmacologie, INSERM U114, Paris, France, 32Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY, USA, 43Institut A. Fessard, CNRS, Gif-sur-Yvette, France
    Search for more papers by this author
  • J-D. Vincent,

    1. 1 Brain Research Unit, Université Libre de Bruxelles, Brussels, Belgium, 21Collège de France, Chaire de Neuropharmacologie, INSERM U114, Paris, France, 32Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY, USA, 43Institut A. Fessard, CNRS, Gif-sur-Yvette, France
    Search for more papers by this author
  • J-J. Vanderhaeghen,

    1. 1 Brain Research Unit, Université Libre de Bruxelles, Brussels, Belgium, 21Collège de France, Chaire de Neuropharmacologie, INSERM U114, Paris, France, 32Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY, USA, 43Institut A. Fessard, CNRS, Gif-sur-Yvette, France
    Search for more papers by this author
  • J-A. Girault

    1. 1 Brain Research Unit, Université Libre de Bruxelles, Brussels, Belgium, 21Collège de France, Chaire de Neuropharmacologie, INSERM U114, Paris, France, 32Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY, USA, 43Institut A. Fessard, CNRS, Gif-sur-Yvette, France
    Search for more papers by this author

Correspondence: Dr Serge N. Schiffmann, Brain Research Unit and Laboratory of Neuropathology and Neuropeptides Research, Université Libre de Bruxelles, Campus Erasme, CP 601, 808 route de Lennik, 1070 Brussels, Belgium. E-mail: sschiffm@ulb.ac.be

Abstract

DARPP-32 is a cyclic adenosine monophosphate-regulated inhibitor of protein phosphatase 1, highly enriched in striatonigral neurons. Stimulation of dopamine D1 receptors increases phosphorylation of DARPP-32, whereas glutamate acting on N-methyl-d-aspartate receptors induces its dephosphorylation. Yet, to date, there is little direct evidence for the function of DARPP-32 in striatal neurons. Using a whole cell patch-clamp technique, we have studied the role of DARPP-32 in the regulation of voltage-gated sodium channels in rat striatal neurons maintained in primary culture. Injection of phospho-DARPP-32, but not of the unphosphorylated form, reduced the sodium current amplitude. This effect was similar to those induced by okadaic acid, with which there was no additivity and by tautomycin. Our results indicate that, in striatal neurons, sodium channels are under dynamic control by phosphorylation/dephosphorylation, and that phospho-DARPP-32 reduces sodium current by stabilizing a phosphorylated state of the channel or an associated regulatory protein. We propose that the DARPP-32-mediated modulation of sodium channels, via inhibition of phosphatase 1, contributes to the regulation of these channels by D1 receptors and other neurotransmitters which influence the state of phosphorylation of DARPP-32.

Ancillary