Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons

Science. 2012 Aug 17;337(6096):839-42. doi: 10.1126/science.1222826. Epub 2012 Aug 2.

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.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ARNTL Transcription Factors / genetics
  • Animals
  • Circadian Rhythm*
  • Fluorometry
  • Glutathione / metabolism
  • Membrane Potentials
  • Mice
  • Mice, Mutant Strains
  • NADP / metabolism
  • Neurons / metabolism
  • Neurons / physiology*
  • Oxidation-Reduction
  • Potassium Channels / metabolism
  • Rats
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / metabolism
  • Suprachiasmatic Nucleus / physiology*

Substances

  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Potassium Channels
  • NADP
  • Glutathione