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J Biol Rhythms. 2014 Aug;29(4):288-98. doi: 10.1177/0748730414540453.

A specific role for the REV-ERBα-controlled L-Type Voltage-Gated Calcium Channel CaV1.2 in resetting the circadian clock in the late night.

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Department of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
MRC Laboratory of Molecular Biology, Cambridge, UK.
Institute of Pharmacology and Toxicology, TU Munich, Munich, Germany.
Department of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland


Within the suprachiasmatic nucleus (SCN) of the hypothalamus, circadian timekeeping and resetting have been shown to be largely dependent on both membrane depolarization and intracellular second-messenger signaling. In both of these processes, voltage-gated calcium channels (VGCCs) mediate voltage-dependent calcium influx, which propagates neural impulses by stimulating vesicle fusion and instigates intracellular pathways resulting in clock gene expression. Through the cumulative actions of these processes, the phase of the internal clock is modified to match the light cycle of the external environment. To parse out the distinct roles of the L-type VGCCs, we analyzed mice deficient in Cav1.2 (Cacna1c) in brain tissue. We found that mice deficient in the Cav1.2 channel exhibited a significant reduction in their ability to phase-advance circadian behavior when subjected to a light pulse in the late night. Furthermore, the study revealed that the expression of Cav1.2 mRNA was rhythmic (peaking during the late night) and was regulated by the circadian clock component REV-ERBα. Finally, the induction of clock genes in both the early and late subjective night was affected by the loss of Cav1.2, with reductions in Per2 and Per1 in the early and late night, respectively. In sum, these results reveal a role of the L-type VGCC Cav1.2 in mediating both clock gene expression and phase advances in response to a light pulse in the late night.


L-type calcium channel; REV-ERBα; calcium; light; resetting; suprachiasmatic nucleus (SCN)

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