The end effector of circadian heart rate variation: The sinoatrial node pacemaker cell

Yael Yaniv, Edward G. Lakatta

Research output: Contribution to journalShort surveypeer-review

17 Scopus citations


Cardiovascular function is regulated by the rhythmicity of circadian, infradian and ultradian clocks. Specific time scales of different cell types drive their functions: circadian gene regulation at hours scale, activation-inactivation cycles of ion channels at millisecond scales, the heart's beating rate at hundreds of millisecond scales, and low frequency autonomic signaling at cycles of tens of seconds. Heart rate and rhythm are modulated by a hierarchical clock system: autonomic signaling from the brain releases neurotransmitters from the vagus and sympathetic nerves to the heart's pacemaker cells and activate receptors on the cell. These receptors activating ultradian clock functions embedded within pacemaker cells include sarcoplasmic reticulum rhythmic spontaneous Ca2+ cycling, rhythmic ion channel current activation and inactivation, and rhythmic oscillatory mitochondria ATP production. Here we summarize the evidence that intrinsic pacemaker cell mechanisms are the end effector of the hierarchical brain-heart circadian clock system.

Original languageEnglish
Pages (from-to)677-684
Number of pages8
JournalBMB Reports
Issue number12
StatePublished - 2015


  • Cardiac denervation
  • Coupled-clock pacemaker system
  • Fractal-like behavior
  • Heart rate variability
  • Ultradian rhythm of the heart rate

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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