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Cav1.2, Cacna1c, EEG spectral power, L-type voltage-dependent calcium channel, schizophrenie sleep
Abstract:
Study Objectives: The CACNA1C gene encodes the alpha 1C (alpha(1C))
subunit of the Ca(v)1.2 voltage-dependent L-type calcium channel (LTCC).
Some of the other voltage-dependent calcium channels, e.g., P-/Q-type,
Ca(v)2.1; N-type, Ca(v)2.2; E-/R-type, Ca(v)2.3; and T-type, Ca(v)3.3
have been implicated in sleep modulation. However, the contribution of
LTCCs to sleep remains largely unknown. Based on recent genome-wide
association studies, CACNA1C emerged as one of potential candidate genes
associated with both sleep and psychiatric disorders. Indeed, most
patients with mental illnesses have sleep problems and vice versa.
Design: To investigate an impact of Ca(v)1.2 on sleep-wake behavior and
electroencephalogram (EEG) activity, polysomnography was performed in
heterozygous Cacna1c (HET) knockout mice and their wild-type (WT)
littermates under baseline and challenging conditions (acute sleep
deprivation and restraint stress).
Measurements and Results: HET mice displayed significantly lower EEG
spectral power than WT mice across high frequency ranges (beta to gamma)
during wake and rapid eye movement (REM) sleep. Although HET mice spent
slightly more time asleep in the dark period, daily amounts of sleep did
not differ between the two genotypes. However, recovery sleep after
exposure to both types of challenging stress conditions differed
markedly; HET mice exhibited reduced REM sleep recovery responses
compared to WT mice.
Conclusions: These results suggest the involvement of Cacna1c (Ca(v)1.2)
in fast electroencephalogram oscillations and REM sleep regulatory
processes. Lower spectral gamma activity, slightly increased sleep
demands, and altered REM sleep responses found in heterozygous Cacna1c
knockout mice may rather resemble a sleep phenotype observed in
schizophrenia patients.
