Circadian redox rhythms in the regulation of neuronal excitability.
نویسندگان
چکیده
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 many 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.
منابع مشابه
Brain circadian oscillators and redox regulation in mammals.
SIGNIFICANCE Functional states of organisms vary rhythmically with a period of about a day (i.e., circadian). This endogenous dynamic is shaped by day-night alternations in light and energy. Mammalian circadian rhythms are orchestrated by the hypothalamic suprachiasmatic nucleus (SCN), a brain region specialized for timekeeping. These autonomous ~24-h oscillations are cell-based, requiring tran...
متن کاملCircadian Rhythms of Redox State and Regulation of Neuronal Excitability in Suprachiasmatic Nucleus of Rodents
متن کامل
Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons.
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 transcrip...
متن کاملMicroRNA-92a is a circadian modulator of neuronal excitability in Drosophila
Many biological and behavioural processes of animals are governed by an endogenous circadian clock, which is dependent on transcriptional regulation. Here we address post-transcriptional regulation and the role of miRNAs in Drosophila circadian rhythms. At least six miRNAs show cycling expression levels within the pigment dispersing factor (PDF) cell-pacemaker neurons; only mir-92a peaks during...
متن کاملRegulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitability
How neurons encode intracellular biochemical signalling cascades into electrical signals is not fully understood. Neurons in the central circadian clock in mammals provide a model system to investigate electrical encoding of biochemical timing signals. Here, using experimental and modelling approaches, we show how the activation of glycogen synthase kinase 3 (GSK3) contributes to neuronal excit...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Free radical biology & medicine
دوره شماره
صفحات -
تاریخ انتشار 2018