Abstract

Oxidation-reduction reactions are essential to life as the core mechanisms of energy transfer. A large body of evidence in recent years presents an extensive and complex network of interactions between the circadian and cellular redox systems. Recent advances show that cellular redox state undergoes a ~24-h (circadian) oscillation in most tissues and is conserved across the domains of life. In nucleated cells, the metabolic oscillation is dependent upon the circadian transcription-translation machinery and, vice versa, redox-active proteins and cofactors feed back into the molecular oscillator. In the suprachiasmatic nucleus (SCN), a hypothalamic region of the brain specialized for circadian timekeeping, redox oscillation was found to modulate neuronal membrane excitability. The SCN redox environment is relatively reduced in daytime when neuronal activity is highest and relatively oxidized in nighttime when activity is at its lowest. There is evidence that the redox environment directly modulates SCN K + channels, tightly coupling metabolic rhythms to neuronal activity. Application of reducing or oxidizing agents produces rapid changes in membrane excitability in a time-of-day-dependent manner. We propose that this reciprocal interaction may not be unique to the SCN. In this review, we consider the evidence for circadian redox oscillation and its interdependencies with established circadian timekeeping mechanisms. Furthermore, we will investigate the effects of redox on ion-channel gating dynamics and membrane excitability. The susceptibility of myriad different ion channels to modulation by changes in the redox environment suggests that circadian redox rhythms may play a role in the regulation of all excitable cells.

Original languageEnglish (US)
Pages (from-to)45-55
Number of pages11
JournalFree Radical Biology and Medicine
Volume119
DOIs
StatePublished - May 1 2018

Fingerprint

Circadian Rhythm
Oxidation-Reduction
Suprachiasmatic Nucleus
Membranes
Ion Channels
Ion Channel Gating
Redox reactions
Reducing Agents
Complex networks
Transcription
Energy Transfer
Oxidants
Energy transfer
Machinery
Brain
Modulation
Tissue
Feedback

Keywords

  • K+ channels
  • brain
  • cellular redox
  • circadian rhythms
  • hypothalamus
  • ion channels
  • neuronal excitability
  • neurophysiology
  • redox
  • suprachiasmatic nucleus

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Circadian redox rhythms in the regulation of neuronal excitability. / Bothwell, Mia Y.; Gillette, Martha L.

In: Free Radical Biology and Medicine, Vol. 119, 01.05.2018, p. 45-55.

Research output: Contribution to journalReview article

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