TY - JOUR
T1 - N-type calcium channel α1B subunit (Cav2.2) Knock-out mice display hyperactivity and vigilance state differences
AU - Beuckmann, Carsten T.
AU - Sinton, Christopher M.
AU - Miyamoto, Norimasa
AU - Ino, Mitsuhiro
AU - Yanagisawa, Masashi
PY - 2003/7/30
Y1 - 2003/7/30
N2 - Differential properties of voltage-dependent Ca2+ channels have been primarily ascribed to the α1 subunit, of which 10 different subtypes are currently known. For example, channels that conduct the N-type Ca2+ current possess the α1B subunit (Cav2.2), which has been localized, inter alia, to the piriform cortex, hippocampus, hypothalamus, locus coeruleus, dorsal raphe, thalamic nuclei, and granular layer of the cortex. Some of these regions have been previously implicated in metabolic and vigilance state control, and selective block of the N-type Ca2+ channel causes circadian rhythm disruption. In this study of Cav2.2-/- knock-out mice, we examined potential differences in feeding behavior, spontaneous locomotion, and the sleep-wake cyde. Cav2.2-/- mice did not display an overt metabolic phenotype but were hyperactive, demonstrating a 20% increase in activity under novel conditions and a 95% increase in activity under habituated conditions during the dark phase, compared with wild-type littermates. Cav2.2-/- mice also displayed vigilance state differences during the light phase, including increased consolidation of rapid-eye movement (REM) sleep and increased intervals between non-REM (NREM) and wakefulness episodes. EEG spectral power was increased during wakefulness and REM sleep and was decreased during NREM sleep in Cav2.2-/- mice. These results indicate a role of the N-type Ca2+ channel in activity and vigilance state control, which we interpret in terms of effects on neurotransmitter release.
AB - Differential properties of voltage-dependent Ca2+ channels have been primarily ascribed to the α1 subunit, of which 10 different subtypes are currently known. For example, channels that conduct the N-type Ca2+ current possess the α1B subunit (Cav2.2), which has been localized, inter alia, to the piriform cortex, hippocampus, hypothalamus, locus coeruleus, dorsal raphe, thalamic nuclei, and granular layer of the cortex. Some of these regions have been previously implicated in metabolic and vigilance state control, and selective block of the N-type Ca2+ channel causes circadian rhythm disruption. In this study of Cav2.2-/- knock-out mice, we examined potential differences in feeding behavior, spontaneous locomotion, and the sleep-wake cyde. Cav2.2-/- mice did not display an overt metabolic phenotype but were hyperactive, demonstrating a 20% increase in activity under novel conditions and a 95% increase in activity under habituated conditions during the dark phase, compared with wild-type littermates. Cav2.2-/- mice also displayed vigilance state differences during the light phase, including increased consolidation of rapid-eye movement (REM) sleep and increased intervals between non-REM (NREM) and wakefulness episodes. EEG spectral power was increased during wakefulness and REM sleep and was decreased during NREM sleep in Cav2.2-/- mice. These results indicate a role of the N-type Ca2+ channel in activity and vigilance state control, which we interpret in terms of effects on neurotransmitter release.
KW - Calcium
KW - EEG
KW - Electroencephalogram
KW - Locomotion
KW - Mouse
KW - REM sleep
KW - Vigilance state
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U2 - 10.1523/jneurosci.23-17-06793.2003
DO - 10.1523/jneurosci.23-17-06793.2003
M3 - Article
C2 - 12890773
AN - SCOPUS:0042133371
SN - 0270-6474
VL - 23
SP - 6793
EP - 6797
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 17
ER -