SK channel blockade promotes burst firing in dorsal raphe serotonergic neurons

Authors

  • Nathalie Rouchet,

    1. Laboratory of Pharmacology and Research Center for Cellular and Molecular Neurobiology, Institute of Pathology 2 (B36), University of Liège, CHU, B-4000 Sart Tilman, Liège, Belgium
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    • *

      N.R. and O.W. contributed equally to this work.

  • Olivier Waroux,

    1. Laboratory of Pharmacology and Research Center for Cellular and Molecular Neurobiology, Institute of Pathology 2 (B36), University of Liège, CHU, B-4000 Sart Tilman, Liège, Belgium
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    • *

      N.R. and O.W. contributed equally to this work.

  • Cédric Lamy,

    1. Laboratory of Pharmacology and Research Center for Cellular and Molecular Neurobiology, Institute of Pathology 2 (B36), University of Liège, CHU, B-4000 Sart Tilman, Liège, Belgium
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  • Laurent Massotte,

    1. Laboratory of Pharmacology and Research Center for Cellular and Molecular Neurobiology, Institute of Pathology 2 (B36), University of Liège, CHU, B-4000 Sart Tilman, Liège, Belgium
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  • Jacqueline Scuvée-Moreau,

    1. Laboratory of Pharmacology and Research Center for Cellular and Molecular Neurobiology, Institute of Pathology 2 (B36), University of Liège, CHU, B-4000 Sart Tilman, Liège, Belgium
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  • Jean-François Liégeois,

    1. Laboratory of Medicinal Chemistry and Drug Research Center, Institute of Pathology 2 (B36), University of Liège, CHU, B-4000 Sart Tilman, Liège, Belgium
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  • Vincent Seutin

    1. Laboratory of Pharmacology and Research Center for Cellular and Molecular Neurobiology, Institute of Pathology 2 (B36), University of Liège, CHU, B-4000 Sart Tilman, Liège, Belgium
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Dr V. Seutin, as above.
E-mail: V.Seutin@ulg.ac.be

Abstract

Previous in vivo studies have shown that blockade of small-conductance Ca2+-activated potassium (SK) channels enhances burst firing in dopaminergic neurons. As bursting has been found to be physiologically relevant for the synaptic release of serotonin (5-HT), we investigated the possible role of SK channels in the control of this firing pattern in 5-HT neurons of the dorsal raphe nucleus. In these cells, bursts are usually composed of doublets consisting of action potentials separated by a small interval (< 20 ms). Both in vivo and in vitro extracellular recordings were performed, using anesthetized rats and rat brain slices, respectively. In vivo, the specific SK blocker UCL 1684 (200 μm) iontophoresed onto presumed 5-HT neurons significantly increased the production of bursts in 13 out of 25 cells. Furthermore, the effect of UCL 1684 persisted in the presence of both the GABAA antagonist SR 95531 (10 mm) and the GABAB antagonist CGP 35348 (10 mm), whereas these agents by themselves did not significantly influence the neuronal firing pattern. In vitro, bath superfusion of the SK channel blocker apamin (300 nm) induced bursting in only three out of 18 neurons, although it increased the coefficient of variation of the interspike intervals in all the other cells. Our results suggest that SK channel blockade promotes bursting activity in 5-HT neurons via a direct action. An input which is present only in vivo seems to be important for the induction of this firing pattern in these cells.

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