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 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.