BK channels regulate spontaneous action potential rhythmicity in the suprachiasmatic nucleus.
BACKGROUND
Circadian ( approximately 24 hr) rhythms are generated by the central pacemaker localized to the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the basis for intrinsic rhythmicity is generally understood to rely on transcription factors encoded by "clock genes", less is known about the daily regulation of SCN neuronal activity patterns that communicate a circadian time signal to downstream behaviors and physiological systems. Action potentials in the SCN are necessary for the circadian timing of behavior, and individual SCN neurons modulate their spontaneous firing rate (SFR) over the daily cycle, suggesting that the circadian patterning of neuronal activity is necessary for normal behavioral rhythm expression. The BK K(+) channel plays an important role in suppressing spontaneous firing at night in SCN neurons. Deletion of the Kcnma1 gene, encoding the BK channel, causes degradation of circadian behavioral and physiological rhythms.


RESULTS
To test the hypothesis that loss of robust behavioral rhythmicity in Kcnma1(-/-) mice is due to the disruption of SFR rhythms in the SCN, we used multi-electrode arrays to record extracellular action potentials from acute wild-type (WT) and Kcnma1(-/-) slices. Patterns of activity in the SCN were tracked simultaneously for up to 3 days, and the phase, period, and synchronization of SFR rhythms were examined. Loss of BK channels increased arrhythmicity but also altered the amplitude and period of rhythmic activity. Unexpectedly, Kcnma1(-/-) SCNs showed increased variability in the timing of the daily SFR peak.


CONCLUSIONS
These results suggest that BK channels regulate multiple aspects of the circadian patterning of neuronal activity in the SCN. In addition, these data illustrate the characteristics of a disrupted SCN rhythm downstream of clock gene-mediated timekeeping and its relationship to behavioral rhythms.
Kent
Jack
J
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Meredith
Andrea L
AL
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004566:Electrodes; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D010805:Physical Conditioning, Animal; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D013997:Time Factors
C465449:Kcnma1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits