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BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output

Nature Neuroscience volume 9, pages 10411049 (2006) | Download Citation

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  • An Erratum to this article was published on 01 September 2006

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Abstract

Spontaneous action potentials in the suprachiasmatic nucleus (SCN) are necessary for normal circadian timing of behavior in mammals. The SCN exhibits a daily oscillation in spontaneous firing rate (SFR), but the ionic conductances controlling SFR and the relationship of SFR to subsequent circadian behavioral rhythms are not understood. We show that daily expression of the large conductance Ca2+-activated K+ channel (BK) in the SCN is controlled by the intrinsic circadian clock. BK channel–null mice (Kcnma1−/−) have increased SFRs in SCN neurons selectively at night and weak circadian amplitudes in multiple behaviors timed by the SCN. Kcnma1−/− mice show normal expression of clock genes such as Arntl (Bmal1), indicating a role for BK channels in SCN pacemaker output, rather than in intrinsic time-keeping. Our findings implicate BK channels as important regulators of the SFR and suggest that the SCN pacemaker governs the expression of circadian behavioral rhythms through SFR modulation.

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  • 03 August 2006

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Acknowledgements

We thank M. Barakat for assistance with circadian behavioral experiments, L. Baxter for assistance with animal care, and V. Cao for SCN slice preparation advice. We also thank D. Welsh for helpful comments on the manuscript. The work was supported by the Howard Hughes Medical Institute (R.W.A. & J.S.T.), the Mathers Foundation (R.W.A.) and the US National Institutes of Health (NIH MH-60385 to N.F.R.).

Author information

Author notes

    • Andrea L Meredith

    Present address: Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, Maryland 21201, USA.

Affiliations

  1. Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.

    • Andrea L Meredith
    • , Steven W Wiler
    • , Anthony A Fodor
    •  & Richard W Aldrich
  2. Department of Neurobiology and Physiology and Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois 60208, USA.

    • Brooke H Miller
    •  & Joseph S Takahashi
  3. Department of Biological Sciences, Stanford University, Stanford, California 94305, USA.

    • Norman F Ruby

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Andrea L Meredith.

Supplementary information

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  1. 1.

    Supplementary Table 1

    Pearson r-squared values for the microarrays. Each probeset on each array was summarized by the median of the Perfect Match (PM) values. Reported is the Pearson correlation between the median values for each WT: Slo−/− pair of arrays in the data set.

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    Supplementary Methods

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DOI

https://doi.org/10.1038/nn1740