title: Ryanodine-sensitive intracellular Ca2+channels are involved in the output from the SCN circadian clock.
abstract: The suprachiasmatic nuclei (SCN) contain the major circadian clock responsible for generation of circadian rhythms in mammals. The time measured by the molecular circadian clock must eventually be translated into a neuronal firing rate pattern to transmit a meaningful signal to other tissues and organs in the animal. Previous observations suggest that circadian modulation of ryanodine receptors (RyR) is a key element of the output pathway from the molecular circadian clock. To directly test this hypothesis, we studied the effects of RyR activation and inhibition on real time expression of PERIOD2::LUCIFERASE, intracellular calcium levels and spontaneous firing frequency in mouse SCN neurons. Furthermore, we determined whether the RyR-2 mRNA is expressed with a daily variation in SCN neurons. We provide evidence that pharmacological manipulation of RyR in mice SCN neurons alters the free [Ca2+]iin the cytoplasm and the spontaneous firing without affecting the molecular clock mechanism. Our data also show a daily variation in RyR-2 mRNA from single mouse SCN neurons with highest levels during the day. Together, these results confirm the hypothesis that RyR-2 is a key element of the circadian clock output from SCN neurons.
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Coyoacan, Mexico City D.F, 04510, México. raguilar@ifc.unam.mx.
authors.forename: Raúl
authors.initials: R
authors.lastname: Aguilar-Roblero
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Coyoacan, Mexico City D.F, 04510, México.
authors.forename: Daniel
authors.initials: D
authors.lastname: Quinto
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla Querétaro, México.
authors.forename: Adrian
authors.initials: A
authors.lastname: Báez-Ruíz
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Coyoacan, Mexico City D.F, 04510, México.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Chávez
authors.affiliation: Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Andrea Carmine
authors.initials: AC
authors.lastname: Belin
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla Querétaro, México.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Díaz-Muñoz
authors.affiliation: Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Stephan
authors.initials: S
authors.lastname: Michel
authors.affiliation: Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lundkvist
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000187:drug effects* / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D056950:Period Circadian Proteins / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000502:physiology
chemical_list: D056950:Period Circadian Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine
keywords: C57/Bl6 mice; PERIOD 2; biological clock; calcium release; cell signaling