title: An unexpected role for TASK-3 potassium channels in network oscillations with implications for sleep mechanisms and anesthetic action.
abstract: TASK channels are acid-sensitive and anesthetic-activated members of the family of two-pore-domain potassium channels. We have made the surprising discovery that the genetic ablation of TASK-3 channels eliminates a specific type of theta oscillation in the cortical electroencephalogram (EEG) resembling type II theta (4-9 Hz), which is thought to be important in processing sensory stimuli before initiating motor activity. In contrast, ablation of TASK-1 channels has no effect on theta oscillations. Despite the absence of type II theta oscillations in the TASK-3 knockout (KO) mice, the related type I theta, which has certain neuronal pathways in common and is involved in exploratory behavior, is unaffected. In addition to the absence of type II theta oscillations, the TASK-3 KO animals show marked alterations in both anesthetic sensitivity and natural sleep behavior. Their sensitivity to halothane, a potent activator of TASK channels, is greatly reduced, whereas their sensitivity to cyclopropane, which does not activate TASK-3 channels, is unchanged. The TASK-3 KO animals exhibit a slower progression from their waking to sleeping states and, during their sleeping period, their sleep episodes as well as their REM theta oscillations are more fragmented. These results imply a previously unexpected role for TASK-3 channels in the cellular mechanisms underlying these behaviors and suggest that endogenous modulators of these channels may regulate theta oscillations.
authors.affiliation: Biophysics Section, Blackett Laboratory, Imperial College, South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Daniel S J
authors.initials: DS
authors.lastname: Pang
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Robledo
authors.forename: David R
authors.initials: DR
authors.lastname: Carr
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Gent
authors.forename: Alexei L
authors.initials: AL
authors.lastname: Vyssotski
authors.forename: Alex
authors.initials: A
authors.lastname: Caley
authors.forename: Anna Y
authors.initials: AY
authors.lastname: Zecharia
authors.forename: William
authors.initials: W
authors.lastname: Wisden
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Brickley
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Franks
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D004569:Electroencephalography; D004576:Electromyography; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D009991:Oscillometry; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency / Q000235:genetics*; D012890:Sleep / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology
chemical_list: D024683:Potassium Channels, Tandem Pore Domain