RT Journal Article SR Electronic T1 A Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 7682 OP 7686 DO 10.1523/JNEUROSCI.2211-05.2005 VO 25 IS 33 A1 Gabriella B. Lundkvist A1 Yongho Kwak A1 Erin K. Davis A1 Hajime Tei A1 Gene D. Block YR 2005 UL http://www.jneurosci.org/content/25/33/7682.abstract AB Generation of mammalian circadian rhythms involves molecular transcriptional and translational feedback loops. It is not clear how membrane events interact with the intracellular molecular clock or whether membrane activities are involved in the actual generation of the circadian rhythm. We examined the role of membrane potential and calcium (Ca2+) influx in the expression of the circadian rhythm of the clock gene Period 1 (Per1) within the rat suprachiasmatic nucleus (SCN), the master pacemaker controlling circadian rhythmicity. Membrane hyperpolarization, caused by lowering the extracellular concentration of potassium or blocking Ca2+ influx in SCN cultures by lowering [Ca2+], reversibly abolished the rhythmic expression of Per1. In addition, the amplitude of Per1 expression was markedly decreased by voltage-gated Ca2+ channel antagonists. A similar result was observed for mouse Per1 and PER2. Together, these results strongly suggest that a transmembrane Ca2+ flux is necessary for sustained molecular rhythmicity in the SCN. We propose that periodic Ca2+ influx, resulting from circadian variations in membrane potential, is a critical process for circadian pacemaker function.