Circadian regulation and function of voltage-dependent calcium channels in the suprachiasmatic nucleus.
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 alpha1 subunits. The rat SCN and SCN2.2 cells exhibited mRNA expression for all major types of VDCC alpha1 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.
Nahm
Sang-Soep
SS
Department of Human Anatomy and Medical Neurobiology, College of Medicine, Texas A&M University Health Science Center, College Station, Texas 77843-1114, USA.
Farnell
Yuhua Z
YZ
Griffith
William
W
Earnest
David J
DJ
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002104:Cadmium / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D056950:Period Circadian Proteins; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013493:Suprachiasmatic Nucleus / Q000166:cytology* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D002104:Cadmium; D015220:Calcium Channels; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D014157:Transcription Factors; C538960:BMAL1 protein, human; C513311:Per2 protein, rat