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Adaptive regulation of neuronal excitability by a voltage- independent potassium conductance

Nature volume 409, pages 8892 (04 January 2001) | Download Citation

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Abstract

Many neurons receive a continuous, or ‘tonic’, synaptic input, which increases their membrane conductance, and so modifies the spatial and temporal integration of excitatory signals1,2,3. In cerebellar granule cells, although the frequency of inhibitory synaptic currents is relatively low, the spillover of synaptically released GABA (γ-aminobutyric acid)4 gives rise to a persistent conductance mediated by the GABA A receptor5,6,7 that also modifies the excitability of granule cells8. Here we show that this tonic conductance is absent in granule cells that lack the α6 and δ-subunits of the GABAA receptor. The response of these granule cells to excitatory synaptic input remains unaltered, owing to an increase in a ‘leak’ conductance, which is present at rest, with properties characteristic of the two-pore-domain K+ channel TASK-1 (refs 9,10,11,12). Our results highlight the importance of tonic inhibition mediated by GABAA receptors, loss of which triggers a form of homeostatic plasticity leading to a change in the magnitude of a voltage-independent K + conductance that maintains normal neuronal behaviour.

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Acknowledgements

Supported by a Wellcome Trust Programme grant to S.G.C.-C. and a Human Frontier Science Program grant to W.W. We thank L. Cathala, B. Clark, M. Häusser, S.-Q. Liu, T. Takahashi and D. Wyllie for comments on the manuscript, and A. Mathie and B. Robertson for valuable discussion.

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  1. *Department of Pharmacology, University College London, London WC1E 6BT, UK

    • Stephen G. Brickley
    • , Stuart G. Cull-Candy
    •  & Mark Farrant
  2. †Medical Research Council Laboratory of Molecular Biology, Medical Research Council Centre, Cambridge CB2 2QH, UK

    • Victoria Revilla
    •  & William Wisden

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Correspondence to Mark Farrant.

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https://doi.org/10.1038/35051086

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