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The effect of transgenic manipulation of the BK channel on circadian rhythmicity in mice
Author(s) -
Wright Breanne N.,
Meredith Andrea L.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1061.2
Subject(s) - circadian rhythm , per1 , suprachiasmatic nucleus , clock , circadian clock , medicine , endocrinology , biology , bk channel , light effects on circadian rhythm , neuroscience , potassium channel
The aim of our research is to understand how BK Ca 2+ and voltage‐activated K + channels expressed in the suprachiasmatic nucleus (SCN), the brain's master clock, control circadian behavioral activity. Loss of the BK channel gene ( Kcnma1 − / − , BK KO) disrupts the expression of circadian time, mediated by the daily patterning of action potentials in the SCN. To further understand how the BK channel regulates circadian rhythmicity, we analyzed the effect of a transgene containing a gain‐of‐function point mutation in the voltage‐sensor of the channel ( Per1:R207Q ). We hypothesized that alteration of the BK current in the SCN by expression of one or two copies (1C, 2C) of Per1:R207Q on a wild‐type background or one copy of Per1:R207Q with one deleted endogenous copy of Kcnma1 (1C; BK het) would disrupt circadian rhythms, measured with wheel‐running behavior. In contrast, 1C, 2C, and 1C; BK het mice all had relatively normal circadian rhythms. However, we found that compared to WT, adding one copy of Per1:R207Q altered the robustness of the circadian rhythm and caused a longer active interval. The disruption of distinct circadian parameters by expression of Per1:R207Q suggests that BK channels are important for generating normal circadian rhythmicity. A better understanding of the neural encoding of circadian rhythms may impact the treatment of sleep and other disorders of circadian rhythmicity.