A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability

Matthieu Flourakis, Elzbieta Kula-Eversole, Alan L. Hutchison, Tae Hee Han, Kimberly Aranda, Devon L. Moose, Kevin P. White, Aaron R. Dinner, Bridget C Lear, Dejian Ren, Casey O. Diekman, Indira M Raman, Ravi Allada*

*Corresponding author for this work

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Summary Circadian clocks regulate membrane excitability in master pacemaker neurons to control daily rhythms of sleep and wake. Here, we find that two distinctly timed electrical drives collaborate to impose rhythmicity on Drosophila clock neurons. In the morning, a voltage-independent sodium conductance via the NA/NALCN ion channel depolarizes these neurons. This current is driven by the rhythmic expression of NCA localization factor-1, linking the molecular clock to ion channel function. In the evening, basal potassium currents peak to silence clock neurons. Remarkably, daily antiphase cycles of sodium and potassium currents also drive mouse clock neuron rhythms. Thus, we reveal an evolutionarily ancient strategy for the neural mechanisms that govern daily sleep and wake.

Original languageEnglish (US)
Article number8351
Pages (from-to)836-848
Number of pages13
JournalCell
Volume162
Issue number4
DOIs
StatePublished - Aug 17 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Flourakis, M., Kula-Eversole, E., Hutchison, A. L., Han, T. H., Aranda, K., Moose, D. L., White, K. P., Dinner, A. R., Lear, B. C., Ren, D., Diekman, C. O., Raman, I. M., & Allada, R. (2015). A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability. Cell, 162(4), 836-848. [8351]. https://doi.org/10.1016/j.cell.2015.07.036