Intracellular free Ca2+ regulates diverse cellular processes, including membrane potential, neurotransmitter release, and gene expression. To examine the cellular mechanisms underlying the generation of circadian rhythms, nucleus-targeted and untargeted cDNAs encoding a Ca2+-sensitive fluorescent protein (cameleon) were transfected into organotypic cultures of mouse suprachiasmatic nucleus (SCN), the primary circadian pacemaker. Circadian rhythms in cytosolic but not nuclear Ca2+ concentration were observed in SCN neurons. The cytosolic Ca2+ rhythm period matched the circadian multiple-unit-activity (MUA)-rhythm period monitored using a multiple-electrode array, with a mean advance in phase of 4 hr. Tetrodotoxin blocked MUA, but not Ca2+ rhythms, while ryanodine damped both Ca2+ and MUA rhythms. These results demonstrate cytosolic Ca2+ rhythms regulated by the release of Ca2+ from ryanodine-sensitive stores in SCN neurons.
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