A New Approach of Membrane Clock Regulation and Influence on Day-Night Rhythm

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Circadian clock

Circadian clock is a system that regulates a wide spectrum of processes within the body including the molecular, physiological, genetic and behavioural, round the clock (24 hours). These oscillatory mechanisms promote the organisms to adapt and change according to the environment. Evidence shows that expression of genes changes in mammals in a circadian pattern.

Components of membrane clock

The membrane clock consists of four key elements:

  1. A central clock programmed for 24 hours
  2. Signals and pathways that provide input to the central clock, facilitating its interaction with the environment
  3. A wide spectrum of output pathways such as autonomic nervous system and hormones that regulate specific mechanisms of the central clock
  4. Molecular clocks present in different cells associated with the expression of transcriptome, and underlying processes of all the cells

According to Pennartz et al., there are two classes of SCN neurons, class I and class II, that present with spontaneous firing rates. It is believed that these neurons are controlled by potassium currents mediated by calcium that makes them the pacemaker cells of the SCN. Based on the variation in the firing frequency of two classes of SCN neurons, release of various neuropeptide may vary, thereby affecting the circadian-relevant genes and circadian rhythm.

Circadian clock and day-night regulation

An interaction between the circadian clock neurons and clock output molecules has been linked with the sleep circadian regulation. Liu et al. observed that in response to CLK oscillations, the circadian output molecule, WAKE responded, resulting in a decreased excitability of wake-promoting molecules (l-LNVs). Evidence shows that this pathway also stimulates GABA-A receptor refractory to dieldrin (RDL). Similarly, in mammals, mammalian homolog of WAKE exists, mWAKE that is present in the dorsal medial hypothalamus and SCN. Data suggests that mWAKE modulates firing rates and drives wakefulness.

A combination of previously published model led to the development of a novel SCN model, including the electrophysiology model, the molecular clock model, the GABA coupling model, and the VIP coupling model. This model can be a useful approach where the SCN network was integrated into other models. It helped to study the electrical and molecular activities of a single SCN neuron, process of synchronization and integrated network between the different neurons.

The model proved effective in determining the role of GABA as an important neurotransmitter in synchronizing the circadian clock within neurons of the SCN. Additionally, evidence found that it allowed identification of encoding processes within the SCN neurons, especially related to the length of the day. Computational modelling is providing a structure to conduct experiments, promoting understanding of circadian oscillator and cell cycle at a cellular level. This will improve the manner by which future models are developed for gaining insights of circadian associated genes and importance of cell-autonomous mammalian circadian oscillator (CACO) in mammals.

Conclusion

To conclude, the oscillatory dynamics of species are complex and regulated by neurotransmitters, hormones, brain networks that are mediated by environmental stimuli to some extent. Periodic oscillations are a result of an interaction between the network of genes that have been discussed in the present article. The role of cell cycle circadian rhythm needs further experimental models to gain a better understanding regarding the exact mechanism and structural differences between species

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