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Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock

Abstract

The central biological clock of the mammalian brain is located in the suprachiasmatic nucleus. This hypothalamic region contains neurons that generate a circadian rhythm on a single-cell basis. Clock cells transmit their circadian timing signals to other brain areas by diurnal modulation of their spontaneous firing rate. The intracellular mechanism underlying rhythm generation is thought to consist of one or more self-regulating molecular loops, but it is unknown how these loops interact with the plasma membrane to modulate the ionic conductances that regulate firing behaviour. Here we demonstrate a diurnal modulation of Ca2+ current in suprachiasmatic neurons. This current strongly contributes to the generation of spontaneous oscillations in membrane potential, which occur selectively during daytime and are tightly coupled to spike generation. Thus, day–night modulation of Ca2+ current is a central step in transducing the intracellular cycling of molecular clocks to the rhythm in spontaneous firing rate.

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Figure 1: Properties of membrane potential oscillations in SCN.
Figure 2: Role of Ca2+ channels in mediating daytime oscillations.
Figure 3: Diurnal modulation of Ca2+ current in SCN.
Figure 4: Differential effect of nimodipine on spontaneous firing of SCN neurons during the day and night.

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Acknowledgements

We thank G. Borst, J. Meijer, T. Mulder, S. Taverna and M. Verhage for their comments on the manuscript and F. Lopes da Silva for his stimulating advice. This work was supported by the Netherlands Organization for Scientific Research (NWO).

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Correspondence to Cyriel M. A. Pennartz.

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Pennartz, C., de Jeu, M., Bos, N. et al. Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock. Nature 416, 286–290 (2002). https://doi.org/10.1038/nature728

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