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. In cerebellar granule cells, although the frequency of inhibitory synaptic currents is relatively low, the spillover of synaptically released GABA (gamma-aminobutyric acid) gives rise to a persistent conductance mediated by the GABA A receptor that also modifies the excitability of granule cells. 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 9,10,11,12). 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.
Brickley
S G
SG
Department of Pharmacology, University College London, London WC1E 6BT, UK.
Revilla
V
V
Cull-Candy
S G
SG
Wisden
W
W
Farrant
M
M
D000222:Adaptation, Physiological; D000818:Animals; D002531:Cerebellum / Q000166:cytology; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain; D011724:Pyridazines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011724:Pyridazines; D011963:Receptors, GABA-A; C420132:potassium channel subfamily K member 3; D005680:gamma-Aminobutyric Acid; C049853:gabazine; D011188:Potassium