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Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
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Updated: Aug 23, 2025

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
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Coupling-dependent metabolic ultradian rhythms in confluent cells.

Shuzhang Yang1,2, Shin Yamazaki1, Kimberly H Cox1

  • 1Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111.

Proceedings of the National Academy of Sciences of the United States of America
|November 2, 2022
PubMed
Summary

Researchers discovered temperature-sensitive ultradian rhythms in mammalian cells, independent of the cell cycle and circadian clock. These metabolic rhythms are synchronized by cell-to-cell communication via gap junctions.

Keywords:
cellular metabolismgap junctionsion channelsmembrane potentialultradian rhythms

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Area of Science:

  • Cell Biology
  • Metabolic Rhythms
  • Mammalian Physiology

Background:

  • Ultradian rhythms in mammalian metabolism and physiology are known but poorly understood.
  • Mechanisms driving these rapid biological rhythms remain elusive.

Purpose of the Study:

  • To investigate the mechanisms underlying ultradian rhythms in mammalian fibroblasts.
  • To determine if these rhythms are linked to the cell cycle or circadian clock.

Main Methods:

  • Utilized mammalian fibroblast cultures to observe metabolic and physiological parameters.
  • Employed gap junction inhibitors and metabolic assays to probe rhythm synchronization and requirements.
  • Measured parameters including plasma membrane potential, intracellular metabolites (glutamine, α-ketoglutarate, ATP), pH, and calcium.

Main Results:

  • Discovered temperature-sensitive ultradian rhythms (3-24 h period) in fibroblasts, independent of cell cycle and circadian clock.
  • Demonstrated synchronization of single-cell metabolic pulses into stable rhythms via gap junction-mediated coupling.
  • Observed coordinated rhythms in plasma membrane potential, intracellular metabolites, pH, and calcium.

Conclusions:

  • Cellular coupling and metabolic feedback mechanisms, particularly involving glutamine and α-ketoglutarate, are crucial for ultradian rhythm stability.
  • These rhythms may represent a cellular strategy for balancing energy demands and ensuring survival.