A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability.
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.
Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA.
Matthieu
M
Flourakis
Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA.
Elzbieta
E
Kula-Eversole
Medical Scientist Training Program, James Franck Institute, Department of Chemistry, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA.
Alan L
AL
Hutchison
Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA.
Tae Hee
TH
Han
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kimberly
K
Aranda
Department of Biology, University of Iowa, Iowa City, IA 52242, USA.
Devon L
DL
Moose
Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA.
Kevin P
KP
White
Medical Scientist Training Program, James Franck Institute, Department of Chemistry, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA.
Aaron R
AR
Dinner
Department of Biology, University of Iowa, Iowa City, IA 52242, USA.
Bridget C
BC
Lear
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dejian
D
Ren
Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Casey O
CO
Diekman
Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA.
Indira M
IM
Raman
Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA. Electronic address: r-allada@northwestern.edu.
Ravi
R
Allada
D000818:Animals; D001683:Biological Clocks; D002462:Cell Membrane / Q000378:metabolism; D057906:Circadian Clocks; D002940:Circadian Rhythm; D004330:Drosophila / Q000166:cytology / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D029721:Drosophila Proteins; D007473:Ion Channels; D008565:Membrane Proteins; C519922:NALCN protein, mouse; C476573:Na protein, Drosophila; D009419:Nerve Tissue Proteins; D012964:Sodium; D011188:Potassium