Sleep in Kcna2 knockout mice.
BACKGROUND
Shaker codes for a Drosophila voltage-dependent potassium channel. Flies carrying Shaker null or hypomorphic mutations sleep 3-4 h/day instead of 8-14 h/day as their wild-type siblings do. Shaker-like channels are conserved across species but it is unknown whether they affect sleep in mammals. To address this issue, we studied sleep in Kcna2 knockout (KO) mice. Kcna2 codes for Kv1.2, the alpha subunit of a Shaker-like voltage-dependent potassium channel with high expression in the mammalian thalamocortical system.


RESULTS
Continuous (24 h) electroencephalograph (EEG), electromyogram (EMG), and video recordings were used to measure sleep and waking in Kcna2 KO, heterozygous (HZ) and wild-type (WT) pups (P17) and HZ and WT adult mice (P67). Sleep stages were scored visually based on 4-s epochs. EEG power spectra (0-20 Hz) were calculated on consecutive 4-s epochs. KO pups die by P28 due to generalized seizures. At P17 seizures are either absent or very rare in KO pups (< 1% of the 24-h recording time), and abnormal EEG activity is only present during the seizure. KO pups have significantly less non-rapid eye movement (NREM) sleep (-23%) and significantly more waking (+21%) than HZ and WT siblings with no change in rapid eye movement (REM) sleep time. The decrease in NREM sleep is due to an increase in the number of waking episodes, with no change in number or duration of sleep episodes. Sleep patterns, daily amounts of sleep and waking, and the response to 6 h sleep deprivation are similar in HZ and WT adult mice.


CONCLUSIONS
Kv1.2, a mammalian homologue of Shaker, regulates neuronal excitability and affects NREM sleep.
Douglas
Christopher L
CL
Department of Psychiatry, University of Wisconsin, Madison, WI, 53719, USA. cldouglas@wisc.edu
Vyazovskiy
Vladyslav
V
Southard
Teresa
T
Chiu
Shing-Yan
SY
Messing
Albee
A
Tononi
Giulio
G
Cirelli
Chiara
C
D000818:Animals; D004569:Electroencephalography; D004576:Electromyography; D005583:Fourier Analysis; D006579:Heterozygote; D051663:Kv1.2 Potassium Channel / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012890:Sleep / Q000235:genetics*; D012895:Sleep, REM / Q000235:genetics; D014851:Wakefulness / Q000235:genetics
C496970:Kcna2 protein, mouse; D051663:Kv1.2 Potassium Channel