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Fast delayed rectifier potassium current is required for circadian neural activity

Nature Neuroscience volume 8, pages 650–656 (2005)Cite this article

Abstract

In mammals, the precise circadian timing of many biological processes depends on the generation of oscillations in neural activity of pacemaker cells in the suprachiasmatic nucleus (SCN). The ionic mechanisms that underlie these rhythms are largely unknown. Using the mouse brain slice preparation, we show that the magnitude of fast delayed rectifier (FDR) potassium currents has a diurnal rhythm that peaks during the day. Notably, this rhythm continues in constant darkness, providing the first demonstration of the circadian regulation of an intrinsic voltage-gated current in mammalian cells. Blocking this current prevented the daily rhythm in firing rate in SCN neurons. Kv3.1b and Kv3.2 potassium channels were widely distributed within the SCN, with higher expression during the day. We conclude that the FDR is necessary for the circadian modulation of electrical activity in SCN neurons and represents an important part of the ionic basis for the generation of rhythmic output.

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Figure 1: Characterization of SDR K+ currents in SCN neurons.
Figure 2: Characterization of FDR K+ currents in SCN neurons.
Figure 3: Current-voltage relationship of delayed rectifier K+ currents in the mouse dSCN.
Figure 4: Photomicrographs showing immunoreactivity for Kv3.1b and Kv3.2 in the SCN during the day and night.
Figure 5: Blocking FDR currents significantly reduces the firing rate of SCN neurons.
Figure 6: Acutely blocking the FDR current causes significant reduction in firing rate of SCN neurons during the day.
Figure 7: The daily rhythm in the SFR is lost when the FDR current is blocked.

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Acknowledgements

We would like to thank H. Duindam for technical assistance. We would also like to thank E. Herzog and N. Wayne for comments on a draft of the manuscript. Supported by National Institutes of Health grants HL64582, NS043169 and MH68087.

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Authors and Affiliations

  1. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, 760 Westwood Plaza, Los Angeles, 90024-1759, California, USA

    Jason N Itri, Stephan Michel & Christopher S Colwell

  2. Department of Neurophysiology, Leiden University Medical Center, P.O. Box 9604, Leiden, 2300 RC, The Netherlands

    Stephan Michel, Mariska J Vansteensel & Johanna H Meijer

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Correspondence to Christopher S Colwell.

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Itri, J., Michel, S., Vansteensel, M. et al. Fast delayed rectifier potassium current is required for circadian neural activity. Nat Neurosci 8, 650–656 (2005). https://doi.org/10.1038/nn1448

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