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Activation of protein kinase C and inositol 1,4,5-triphosphate receptors antagonistically modulate voltage-gated sodium channels in striatal neurons

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  • Raphaël Hourez, Université Libre de Bruxelles
  • ,
  • Karima Azdad, Université Libre de Bruxelles
  • ,
  • Gilles Vanwalleghem
  • Céline Roussel, Université Libre de Bruxelles
  • ,
  • David Gall, Université Libre de Bruxelles
  • ,
  • Serge N. Schiffmann, Université Libre de Bruxelles

Regulation of voltage-gated sodium channels is crucial to firing patterns that constitute the output of medium spiny neurons (MSN), projecting neurons of the striatum. This modulation is thus critical for the final integration of information processed within the striatum. It has been shown that the adenylate cyclase pathway reduces sodium currents in MSN through channel phosphorylation by cAMP-dependent protein kinase. However, it is unknown whether a phospholipase C (PLC)-mediated signaling cascade could also modulate voltage-gated sodium channels within MSN. Using the whole-cell patch clamp technique, we investigated the effects of activation of two key components in PLC-mediated signaling cascades: protein kinase C (PKC) and inositol-1,4,5-triphosphate (IP 3) receptors on voltage-dependent sodium current. Cellular dialysis with phorbol 12-myristate 13-acetate, an activator of PKC, significantly reduced peak sodium current amplitude, while adenophostin A, an activator of IP 3 receptors, significantly increased peak sodium current amplitude. This effect of adenophostin was abolished by calcium chelation or by FK506, an inhibitor of calcineurin. These results suggest an antagonistic role of PKC and IP3 in the modulation of striatal voltage-gated sodium channels, peak current amplitude being decreased through phosphorylation by PKC and increased through dephosphorylation by calcineurin.

Original languageEnglish
JournalBrain Research
Pages (from-to)189-196
Number of pages8
Publication statusPublished - 19 Oct 2005
Externally publishedYes

Bibliographical note

Funding Information:
The authors wish to thank Dr. David Blum for the helpful pieces of advice and critical reading of the manuscript, Laetitia Cuvelier for the excellent technical assistance, Regis Demeuter for past collaboration on this topic, and Drs. Kadiombo Bantubungi and Hélène Dumont for their support. Raphaël Hourez is a FNRS research fellow (Belgian National Fund for Scientific Research), and Céline Roussel is a FRIA research fellow (Fonds pour la Recherche dans l'Industrie et l'Agriculture). This work was funded by the FNRS (Belgium), FMRE (Belgium), Van Buuren Foundation (Belgium), research funds of ULB (Belgium), and Action de Recherche Concertée (Communauté Française Wallonie-Bruxelles).

    Research areas

  • Calcineurin, IP, PKC, PLC, Striatum, Voltage-dependent sodium channel

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