Circadian regulation of ion channels and their functions

Abstract

Ion channels are the gatekeepers to neuronal excitability. Retinal neurons of vertebrates and invertebrates, neurons of the suprachiasmatic nucleus (SCN) of vertebrates, and pinealocytes of non‐mammalian vertebrates display daily rhythms in their activities. The interlocking transcription–translation feedback loops with specific post‐translational modulations within individual cells form the molecular clock, the basic mechanism that maintains the autonomic ∼24‐h rhythm. The molecular clock regulates downstream output signaling pathways that further modulate activities of various ion channels. Ultimately, it is the circadian regulation of ion channel properties that govern excitability and behavior output of these neurons. In this review, we focus on the recent development of research in circadian neurobiology mainly from 1980 forward. We will emphasize the circadian regulation of various ion channels, including cGMP‐gated cation channels, various voltage‐gated calcium and potassium channels, Na+/K+‐ATPase, and a long‐opening cation channel. The cellular mechanisms underlying the circadian regulation of these ion channels and their functions in various tissues and organisms will also be discussed. Despite the magnitude of chronobiological studies in recent years, the circadian regulation of ion channels still remains largely unexplored. Through more investigation and understanding of the circadian regulation of ion channels, the future development of therapeutic strategies for the treatment of sleep disorders, cardiovascular diseases, and other illnesses linked to circadian misalignment will benefit.

Immunometabolism: Is it under the eye of the clock?

“…However, mRNA expression is just one clock output. Protein modifications including epigenetics [23], subcellular localization [24], rates of translation [25,26] reduction-oxidation (REDOX) [27] and ion concentrations [28] are some of the cellular functions that have been identified as clock regulated.…”

Neurofizjologiczne uwarunkowania procesów snu, czuwania, świadomości i przytomności. Część 2

“…Depolarisation opens further ion channels (L-VGCCs, L-type voltage-gated calcium channels), causing intracellular calcium flux. This in turn activates the cAMP-related pathway, stimulates the synthesis and release of melatonin as well as the recruitment of presynaptic vesicle neurotransmitters contained in receptor cells [34]. In turn, neurons in the SCN have twice the Ca2+ concentration in daytime compared to the night [35].…”

“…REV-ERB αprotein becomes attached to Bmal1 gene promoter, inhibiting the process of gene transcription. These phenomena occur cyclically, corresponding to light and dark phases, with increased stimulation from SCN during daytime and inhibition during the night [34]. Circadian oscillator neurons receive afferent signals from melanopsin-containing cells of the retina, which are the anatomical link between sinusoidal SCN activity and environmental stimuli (light).…”

“…Products of these genes, PERs and CRYs, have inhibitory effects on the transcription of the Bmal-1 gene, thus self-limiting their own concentrations. Proteins are then phosphorylated by protein kinases and undergo degradation, which occurs mostly during daytime [34].…”

Daily rhythmicity of high affinity copper transport

“…Together this creates an environmentally set, endogenous timekeeper that appropriately schedules daily activities, including nutrient transport. 3,4 Transition metals, such as copper (Cu), while being essential nutrients whose requirements vary along the day, are also potentially toxic during intracellular trafficking, owing to their ability to cause oxidative stress. 5,6 Both features, essentiality and toxicity, require fine-tuned and narrow homeostatic mechanisms that, in the case of Cu, are evolutionary conserved.…”