title: BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output.
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 Ca(2+)-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.
authors.affiliation: Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA. ameredith@som.umaryland.edu
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Meredith
authors.forename: Steven W
authors.initials: SW
authors.lastname: Wiler
authors.forename: Brooke H
authors.initials: BH
authors.lastname: Miller
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Takahashi
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fodor
authors.forename: Norman F
authors.initials: NF
authors.lastname: Ruby
authors.forename: Richard W
authors.initials: RW
authors.lastname: Aldrich
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D004594:Electrophysiology; D020869:Gene Expression Profiling; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism
chemical_list: C465449:Kcnma1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits