title: TASK-3 two-pore domain potassium channels enable sustained high-frequency firing in cerebellar granule neurons.
abstract: The ability of neurons, such as cerebellar granule neurons (CGNs), to fire action potentials (APs) at high frequencies during sustained depolarization is usually explained in relation to the functional properties of voltage-gated ion channels. Two-pore domain potassium (K(2P)) channels are considered to simply hyperpolarize the resting membrane potential (RMP) by increasing the potassium permeability of the membrane. However, we find that CGNs lacking the TASK-3 type K(2P) channel exhibit marked accommodation of action potential firing. The accommodation phenotype was not associated with any change in the functional properties of the underlying voltage-gated sodium channels, nor could it be explained by the more depolarized RMP that resulted from TASK-3 channel deletion. A functional rescue, involving the introduction of a nonlinear leak conductance with a dynamic current clamp, was able to restore wild-type firing properties to adult TASK-3 knock-out CGNs. Thus, in addition to the accepted role of TASK-3 channels in limiting neuronal excitability, by increasing the resting potassium conductance TASK-3 channels also increase excitability by supporting high-frequency firing once AP threshold is reached.
authors.affiliation: Biophysics Group, Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom. s.brickley@imperial.ac.uk
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Brickley
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Aller
authors.forename: Cristina
authors.initials: C
authors.lastname: Sandu
authors.forename: Emma L
authors.initials: EL
authors.lastname: Veale
authors.forename: Felicity G
authors.initials: FG
authors.lastname: Alder
authors.forename: Harvinder
authors.initials: H
authors.lastname: Sambi
authors.forename: Alistair
authors.initials: A
authors.lastname: Mathie
authors.forename: William
authors.initials: W
authors.lastname: Wisden
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002531:Cerebellum / Q000166:cytology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000172:deficiency / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C511784:TASK3 protein, mouse; D013779:Tetrodotoxin; D019789:Tetraethylammonium