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

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.