Circadian Rhythm in Heart Cells Uncovered

An MRC study has shown how circadian rhythms in heart cells help to change heart function and may explain why shift workers are more vulnerable to heart problems.

This is the first time that scientists have shown that heart cells regulate their circadian rhythms through daily changes in the levels of ions inside the cell.

Ion concentrations inside the cell were thought to be fairly constant. However, scientists have now found that they alter according to the daily demands of our lives, allowing the heart to better accommodate and sustain increased heart rate when we’re active.

Important new insights

It is already known there are daily clocks in heart cells, and other tissues that are normally synchronised by hormonal signals that align our internal daily rhythms with the day and night cycle.

Daily rhythms of heart function have been known about for years and thought to be due to greater stimulation by the nervous system during the day.

This new study by the Medical Research Council (MRC) Laboratory for Molecular Biology in Cambridge shows circadian rhythms within each heart cell can also affect heart rate. 

Explaining heart problems

The team behind the study say that understanding how these changes in ion levels alter heart function over the day may help to explain why shift workers are more vulnerable to heart problems.

This is because ion rhythms driven by clocks in the heart could get ‘out of sync’ with their stimulation from clocks in the brain.

This new understanding could lead to better treatments and preventative measures for combatting heart conditions.

Developing our understanding

While this study was conducted using cells and mice in the lab, its findings are supported by a recent linked study by collaborators, led by Professor David Bechtold at the University of Manchester.

Their study demonstrated that circadian rhythms in heart rate and electrical activity are clearly evident in both mice and humans. Abrupt changes in behavioural routine or sleep patterns can disturb these normal heart rhythms.

Taken together, these studies suggest that lifestyles that oppose our natural internal clock may cause internal circadian rhythms within heart cells to become de-coupled from our behaviours. This means that heart clocks no longer anticipate the fluctuations in demand that, for most individuals, will be higher in the daytime.

Pushing effective treatments

Dr John O’Neill, from the MRC Laboratory of Molecular Biology, said: "The ways in which heart function changes around the clock turn out to be more complex than previously thought. The ion gradients that contribute to heart rate vary over the daily cycle. This likely helps the heart cope with increased demands during the day, when changes in activity and cardiac output are much greater than at night, when we normally sleep. It opens up the exciting possibility of more effective treatments for cardiovascular conditions, for example by delivering drugs at the right time of day."

Dr Megan Dowie, MRC Head of Molecular and Cellular Medicine, said: "This really interesting research supported through the MRC AstraZeneca Blue Sky Initiative shows the incredible potential for innovative academic-industry relationships to push the frontiers of discovery science. It addresses fundamental, unanswered questions about how the body works and points to exciting new possibilities for therapeutic innovations."

References: 

Stangherlin A, Watson JL, Wong DCS, et al. Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology. 2021;12:6035. doi: 10.1038/s41467-021-25942-4

Hayter EA, Wehrens SMT, Van Dongen HPA, et al. Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia. Nat Commun. 2021;12(1):2472. doi: 10.1038/s41467-021-22788-8

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