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Emerging Concepts in Ion Channel Biophysics
Tuesday Speaker Abstracts
12
Molecular Mechanisms of Circadian Variation in BK Channel Properties
Andrea Meredith
.
University of Maryland School of Medicine, Baltimore, MD, USA.
BK Ca
2+
- and voltage-activated K
+
channels (K
Ca
1.1) regulate excitability in a variety of cell
types, distinctively tuned by several molecular mechanisms including alternative splicing, post-
translational modifications, and protein partnering (accessory subunits and Ca2+ channels). We
investigated the coordination of these mechanisms for the circadian regulation of BK current
properties in the suprachiasmatic nucleus (SCN), the brain’s intrinsic ‘clock.’ The molecular
components that translate the clock mechanism into specific firing patterns during distinct time
windows are just beginning to emerge. In the SCN circuit, BK channels play a central role in the
dynamic regulation of excitability that produces daily oscillations in action potential firing. Our
studies probe the clock-linked regulation of BK channel activity. The day versus night
differences in BK current properties are generated by daily changeovers in BK’s Ca
2+
source,
alternative splicing of the alpha subunit, and beta2 subunit-mediated inactivation. These
mechanisms work in concert to establish BK channel gating as a biophysical switch, toggling
membranes between day and night states, to contribute to the daily variation in SCN excitability
that underlies circadian rhythm.