Circadian dynamics of cytosolic and nuclear Ca2+ in single suprachiasmatic nucleus neurons

Neuron. 2003 Apr 24;38(2):253-63. doi: 10.1016/s0896-6273(03)00164-8.


Intracellular free Ca(2+) regulates diverse cellular processes, including membrane potential, neurotransmitter release, and gene expression. To examine the cellular mechanisms underlying the generation of circadian rhythms, nucleus-targeted and untargeted cDNAs encoding a Ca(2+)-sensitive fluorescent protein (cameleon) were transfected into organotypic cultures of mouse suprachiasmatic nucleus (SCN), the primary circadian pacemaker. Circadian rhythms in cytosolic but not nuclear Ca(2+) concentration were observed in SCN neurons. The cytosolic Ca(2+) rhythm period matched the circadian multiple-unit-activity (MUA)-rhythm period monitored using a multiple-electrode array, with a mean advance in phase of 4 hr. Tetrodotoxin blocked MUA, but not Ca(2+) rhythms, while ryanodine damped both Ca(2+) and MUA rhythms. These results demonstrate cytosolic Ca(2+) rhythms regulated by the release of Ca(2+) from ryanodine-sensitive stores in SCN neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Nucleus / metabolism*
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Culture Techniques / instrumentation
  • Culture Techniques / methods
  • Cytosol / metabolism*
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Microelectrodes
  • Neurons / drug effects
  • Neurons / metabolism*
  • Periodicity
  • Ryanodine / pharmacology
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / drug effects
  • Suprachiasmatic Nucleus / metabolism*
  • Tetrodotoxin / pharmacology
  • Transfection


  • Calcium-Binding Proteins
  • Ryanodine
  • Tetrodotoxin
  • Calcium