In-phasic cytosolic-nuclear Ca rhythms in suprachiasmatic nucleus neurons.

The suprachiasmatic nucleus (SCN) of the hypothalamus is the master circadian clock in mammals. SCN neurons exhibit circadian Ca rhythms in the cytosol, which is thought to act as a messenger linking the transcriptional/translational feedback loop (TTFL) and physiological activities. Transcriptional regulation occurs in the nucleus in the TTFL model, and Ca-dependent kinase regulates the clock gene transcription. However, the Ca regulatory mechanisms between cytosol and nucleus as well as the ionic origin of Ca rhythms remain unclear. In the present study, we monitored circadian-timescale Ca dynamics in the nucleus and cytosol of SCN neurons at the single-cell and network levels. We observed robust nuclear Ca rhythm in the same phase as the cytosolic rhythm in single SCN neurons and entire regions. Neuronal firing inhibition reduced the amplitude of both nuclear and cytosolic Ca rhythms, whereas blocking of Ca release from the endoplasmic reticulum (ER) via ryanodine and inositol 1,4,5-trisphosphate (IP) receptors had a minor effect on either Ca rhythms. We conclude that the in-phasic circadian Ca rhythms in the cytosol and nucleus are mainly driven by Ca influx from the extracellular space, likely through the nuclear pore. It also raises the possibility that nuclear Ca rhythms directly regulate transcription