Document Detail


Mis-expression of the BK K(+) channel disrupts suprachiasmatic nucleus circuit rhythmicity and alters clock-controlled behavior.
MedLine Citation:
PMID:  23174562     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In mammals, almost all aspects of circadian rhythmicity are attributed to activity in a discrete neural circuit of the hypothalamus, the suprachiasmatic nucleus (SCN). A 24-h rhythm in spontaneous firing is the fundamental neural intermediary to circadian behavior, but the ionic mechanisms that pattern circuit rhythmicity, and the integrated impact on behavior, are not well studied. Here, we demonstrate that daily modulation of a major component of the nighttime-phased suppressive K(+) current, encoded by the BK Ca(2+)-activated K(+) current channel (K(Ca)1.1 or Kcnma1), is a critical arbiter of circadian rhythmicity in the SCN circuit. Aberrant induction of BK current during the day in transgenic mice using a Per1 promoter (Tg-BK(R207Q)) reduced SCN firing or silenced neurons, decreasing the circadian amplitude of the ensemble circuit rhythm. Changes in cellular and circuit excitability in Tg-BK(R207Q) SCNs were correlated with elongated behavioral active periods and enhanced responses to phase-shifting stimuli. Unexpectedly, despite the severe reduction in circuit amplitude, circadian behavioral amplitudes in Tg-BK(R207Q) mice were relatively normal. These data demonstrate that downregulation of the BK current during the day is essential for the high amplitude neural activity pattern in the SCN that restricts locomotor activity to the appropriate phase and maintains the clock's robustness against perturbation. However, a residually rhythmic subset prevails over the ensemble circuit to drive the fundamental circadian behavioral rhythm.
Authors:
Jenna R Montgomery; Joshua P Whitt; Breanne N Wright; Michael H Lai; Andrea L Meredith
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-21
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  304     ISSN:  1522-1563     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-18     Completed Date:  2013-04-08     Revised Date:  2014-05-23    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C299-311     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Action Potentials
Amino Acid Substitution
Animals
Behavior, Animal / physiology
Circadian Clocks
Circadian Rhythm*
Gene Expression*
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / genetics*,  metabolism,  physiology
Mice
Mice, Transgenic
Motor Activity
Neurons / metabolism,  physiology
Patch-Clamp Techniques
Suprachiasmatic Nucleus / cytology,  metabolism,  physiology*
Tissue Culture Techniques
Grant Support
ID/Acronym/Agency:
R01 HL102758/HL/NHLBI NIH HHS; R01-HL-102758/HL/NHLBI NIH HHS; R21 DK089337/DK/NIDDK NIH HHS; R21-DK-089337/DK/NIDDK NIH HHS; T32 AR007592/AR/NIAMS NIH HHS; T34 GM008663/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Kcnma1 protein, mouse; 0/Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Comments/Corrections

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