A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability

Cell. 2015 Aug 13;162(4):836-48. doi: 10.1016/j.cell.2015.07.036.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Clocks
  • Cell Membrane / metabolism
  • Circadian Clocks*
  • Circadian Rhythm*
  • Drosophila / cytology
  • Drosophila / physiology*
  • Drosophila Proteins / metabolism
  • Gene Knockdown Techniques
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Sodium / metabolism

Substances

  • Drosophila Proteins
  • Ion Channels
  • NALCN protein, mouse
  • Na protein, Drosophila
  • Nerve Tissue Proteins
  • Sodium
  • Potassium