Circadian Regulation and Function of Voltage-Dependent Calcium Channels in the Suprachiasmatic Nucleus

Abstract

Individual neurons within the suprachiasmatic nuclei (SCNs) are capable of functioning as autonomous clocks and generating circadian rhythms in the expression of genes that form the molecular clockworks. Limited information is available on how these molecular oscillations in individual clock cells are coordinated to provide for the ensemble rhythmicity that is normally observed from the entire SCN. Because calcium influx via voltage-dependent calcium channels (VDCCs) has been implicated in the regulation of gene expression and synchronization of rhythmicity across the population of SCN clock cells, we first examined the rat SCN and an immortalized line of SCN cells (SCN2.2) for expression and circadian regulation of different VDCC ␣1 subunits. The rat SCN and SCN2.2 cells exhibited mRNA expression for all major types of VDCC ␣1 subunits. Relative levels of VDCC expression in the rat SCN and SCN2.2 cells were greatest for L-type channels, moderate for P/Q-and T-type channels, and minimal for R-and N-type channels. Interestingly, both rat SCN and SCN2.2 cells showed rhythmic expression of P/Q-and T-type channels. VDCC involvement in the regulation of molecular rhythmicity in SCN2.2 cells was then examined using the nonselective antagonist, cadmium. The oscillatory patterns of rPer2 and rBmal1 expression were abolished in cadmium-treated SCN2.2 cells without affecting cellular morphology and viability. These findings raise the possibility that the circadian regulation of VDCC activity may play an important role in maintaining rhythmic clock gene expression across an ensemble of SCN oscillators.

Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression

“…7, dotted arrow), leading to Ca 2+ influx in α cells and SNAREmediated release of glucagon granules. Interestingly, multiple genes encoding for VDCC members (Supplemental Table 1) exhibited rhythmic expression, in line with the previously reported circadian regulation of VDCC expression in the SCNs (Nahm et al 2005). Hence, the fact that the activity of VDCCs in islet cells is regulated by glucose makes them good candidates for coupling feeding regimen to intracellular molecular clocks.…”

The expression of L‐type voltage‐gated calcium channels in retinal photoreceptors is under circadian control

“…However, it is controversial as to the precise physiological role of this rhythm in suprachiasmatic nucleus neurons (Pennartz et al 2002;Cloues and Sather 2003;Jackson et al 2004). One possibility is that L-type VGCCs could participate in the circadian input pathway to synchronize the rhythmicity of the expression of clock genes such as Per2 and Bmal1 (Nahm et al 2005). Hence, L-type VGCCs could contribute in coordinating rhythmic clock gene expression through the input pathway, even though the channels themselves are regulated by the circadian clocks and serve as outputs.…”

Calcium Response to Retinohypothalamic Tract Synaptic Transmission in Suprachiasmatic Nucleus Neurons

“…Experiments using blockers of other voltage-gated Ca 2ϩ channels were not preformed because, unlike L-type channels, these channels are heavily expressed on RHT axon terminals (Moldavan et al, 2006). L-type Ca 2ϩ channels in rat SCN contribute to the generation of spontaneous oscillations during the day (Pennartz et al, 2002;Jackson et al, 2004) and have a higher relative level of expression over other voltagedependent Ca 2ϩ channels (Nahm et al, 2005), but the neuronal distribution is not known. Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiation of K ϩ -and glutamateevoked Ca 2ϩ transients in SCN neurons are blocked by nimodipine, suggesting that L-type Ca 2ϩ channels contribute to the regulation of the circadian clock by PACAP (Dziema and Obrietan, 2002).…”