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The Journal of Neuroscience, October 5, 2005, 25(40):9304-9308; doi:10.1523/JNEUROSCI.2733-05.2005

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

Sang-Soep Nahm,¹ Yuhua Z. Farnell,¹ William Griffith,² and David J. Earnest^1,3

Departments of ¹Human Anatomy and Medical Neurobiology and ²Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University Health Science Center, College Station, Texas 77843-1114, and ³Center for Biological Clocks Research, Department of Biology, Texas A&M University, College Station, Texas 77843-3258

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.

Key words: clock; rhythm; SCN2.2; Per2; Bmal1; cadmium

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Received April 12, 2005; revised August 22, 2005; accepted August 31, 2005.

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				R. P. Irwin and C. N. Allen Calcium Response to Retinohypothalamic Tract Synaptic Transmission in Suprachiasmatic Nucleus Neurons J. Neurosci., October 24, 2007; 27(43): 11748 - 11757. [Abstract] [Full Text] [PDF]

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