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

Andrea L. Meredith, Steven W. Wiler, Brooke H. Miller, Joseph S. Takahashi, Anthony A. Fodor, Norman F. Ruby, Richard W. Aldrich

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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.

Original languageEnglish (US)
Pages (from-to)1041-1049
Number of pages9
JournalNature Neuroscience
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 2006

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Meredith, A. L., Wiler, S. W., Miller, B. H., Takahashi, J. S., Fodor, A. A., Ruby, N. F., & Aldrich, R. W. (2006). BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output. Nature Neuroscience, 9(8), 1041-1049. https://doi.org/10.1038/nn1740