A neuronal ryanodine receptor mediates light-induced phase delays of the circadian clock

Nature. 1998 Jul 23;394(6691):381-4. doi: 10.1038/28639.


Circadian clocks are complex biochemical systems that cycle with a period of approximately 24 hours. They integrate temporal information regarding phasing of the solar cycle, and adjust their phase so as to synchronize an organism's internal state to the local environmental day and night. Nocturnal light is the dominant regulator of this entrainment. In mammals, information about nocturnal light is transmitted by glutamate released from retinal projections to the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Clock resetting requires the activation of ionotropic glutamate receptors, which mediate Ca2+ influx. The response induced by such activation depends on the clock's temporal state: during early night it delays the clock phase, whereas in late night the clock phase is advanced. To investigate this differential response, we sought signalling elements that contribute solely to phase delay. We analysed intracellular calcium-channel ryanodine receptors, which mediate coupled Ca2+ signalling. Depletion of intracellular Ca2+ stores during early night blocked the effects of glutamate. Activators of ryanodine receptors induced phase resetting only in early night; inhibitors selectively blocked delays induced by light and glutamate. These findings implicate the release of intracellular Ca2+ through ryanodine receptors in the light-induced phase delay of the circadian clock restricted to the early night.

Publication types

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

MeSH terms

  • Animals
  • Biological Clocks / radiation effects
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Circadian Rhythm* / radiation effects
  • Cricetinae
  • Darkness
  • Glutamic Acid / pharmacology
  • In Vitro Techniques
  • Light*
  • Male
  • Mesocricetus
  • Neurons / physiology*
  • Polyenes / pharmacology
  • Rats
  • Ryanodine Receptor Calcium Release Channel / physiology*
  • Signal Transduction
  • Sirolimus
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / physiology
  • Tacrolimus / pharmacology


  • Calcium Channel Blockers
  • Polyenes
  • Ryanodine Receptor Calcium Release Channel
  • Caffeine
  • Glutamic Acid
  • Calcium
  • Sirolimus
  • Tacrolimus