Coupling-dependent metabolic ultradian rhythms in confluent cells.

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.