title: 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.
abstract: 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.
authors.affiliation: Department of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schmutz
authors.affiliation: Department of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Rohit
authors.initials: R
authors.lastname: Chavan
authors.affiliation: Department of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Ripperger
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Maywood
authors.affiliation: Institute of Pharmacology and Toxicology, TU Munich, Munich, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Langwieser
authors.affiliation: Institute of Pharmacology and Toxicology, TU Munich, Munich, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Jurik
authors.affiliation: Department of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Stauffer
authors.affiliation: Department of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland.
authors.forename: James E
authors.initials: JE
authors.lastname: Delorme
authors.affiliation: Institute of Pharmacology and Toxicology, TU Munich, Munich, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Moosmang
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hastings
authors.affiliation: Institute of Pharmacology and Toxicology, TU Munich, Munich, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.affiliation: Department of Biology, Unit of Biochemistry, University of Fribourg, Fribourg, Switzerland urs.albrecht@unifr.ch.
authors.forename: Urs
authors.initials: U
authors.lastname: Albrecht
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics*; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics*; D056950:Period Circadian Proteins / Q000235:genetics; D017440:Photoperiod; D012333:RNA, Messenger / Q000235:genetics; D013493:Suprachiasmatic Nucleus / Q000502:physiology
chemical_list: C514350:CACNA1C protein, mouse; D020746:Calcium Channels, L-Type; C498262:Nr1d1 protein, mouse; D009687:Nuclear Proteins; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D002118:Calcium
keywords: L-type calcium channel; REV-ERBα; calcium; light; resetting; suprachiasmatic nucleus (SCN)