An unexpected role for TASK-3 potassium channels in network oscillations with implications for sleep mechanisms and anesthetic action.
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.
Pang
Daniel S J
DS
Biophysics Section, Blackett Laboratory, Imperial College, South Kensington, London SW7 2AZ, United Kingdom.
Robledo
Christian J
CJ
Carr
David R
DR
Gent
Thomas C
TC
Vyssotski
Alexei L
AL
Caley
Alex
A
Zecharia
Anna Y
AY
Wisden
William
W
Brickley
Stephen G
SG
Franks
Nicholas P
NP
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
D024683:Potassium Channels, Tandem Pore Domain