title: Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons.
abstract: Daily rhythms of mammalian physiology, metabolism, and behavior parallel the day-night cycle. They are orchestrated by a central circadian clock in the brain, the suprachiasmatic nucleus (SCN). Transcription of clock genes is sensitive to metabolic changes in reduction and oxidation (redox); however, circadian cycles in protein oxidation have been reported in anucleate cells, where no transcription occurs. We investigated whether the SCN also expresses redox cycles and how such metabolic oscillations might affect neuronal physiology. We detected self-sustained circadian rhythms of SCN redox state that required the molecular clockwork. The redox oscillation could determine the excitability of SCN neurons through nontranscriptional modulation of multiple potassium (K(+)) channels. Thus, dynamic regulation of SCN excitability appears to be closely tied to metabolism that engages the clockwork machinery.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Tongfei A
authors.initials: TA
authors.lastname: Wang
authors.forename: Yanxun V
authors.initials: YV
authors.lastname: Yu
authors.forename: Gubbi
authors.initials: G
authors.lastname: Govindaiah
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ye
authors.forename: Liana
authors.initials: L
authors.lastname: Artinian
authors.forename: Todd P
authors.initials: TP
authors.lastname: Coleman
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Sweedler
authors.forename: Charles L
authors.initials: CL
authors.lastname: Cox
authors.forename: Martha U
authors.initials: MU
authors.lastname: Gillette
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D000818:Animals; D002940:Circadian Rhythm; D005470:Fluorometry; D005978:Glutathione / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008817:Mice, Mutant Strains; D009249:NADP / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D015221:Potassium Channels; D009249:NADP; D005978:Glutathione