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

S. G. Brickley, V. Revilla, S. G. Cull-Candy, William Wisden, M. Farrant

    Research output: Contribution to journalArticle

    451 Citations (Scopus)

    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 signals(1-3). In cerebellar granule cells, although the frequency of inhibitory synaptic currents is relatively low, the spillover of synaptically released GABA (gamma -aminobutyric acid)(4) gives rise to a persistent conductance mediated by the GABA(A) receptor(5-7) that also modifies the excitability of granule cells(8). Here we show that this tonic conductance is absent in granule cells that lack the alpha6 and delta -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- 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.

    Original languageEnglish
    Pages (from-to)88-92
    Number of pages4
    JournalNature
    Volume409
    DOIs
    Publication statusPublished - Jan 2001

    Keywords

    • CEREBELLAR GRANULE NEURONS
    • DOMAIN K+ CHANNEL
    • GABA(A) RECEPTORS
    • RAT CEREBELLUM
    • SYNAPTIC INTEGRATION
    • ALPHA-6 SUBUNIT
    • GOLGI CELLS
    • CURRENTS
    • INHIBITION
    • ACTIVATION

    Cite this

    Brickley, S. G., Revilla, V., Cull-Candy, S. G., Wisden, W., & Farrant, M. (2001). Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance. Nature, 409, 88-92. https://doi.org/10.1038/35051086