Home Cellular health Scientists find circadian rhythm in heart cells that affects their daily function

Scientists find circadian rhythm in heart cells that affects their daily function



Heart clocks regulate the daily variation in heart rate – Each heart cell has a clock that regulates the frequency of the discharge rate between day and night. It helps the heart to beat faster during the day and to support daily activities. Credit: Copyright MRC LMB

A new study has shown how circadian rhythms in heart cells help alter heart function throughout the day and may explain why shift workers are more vulnerable to heart problems.

Scientists have shown for the first time that heart cells regulate their circadian rhythms through daily changes in sodium levels and potassium ions inside the cell. The different levels of sodium and potassium ions inside and outside the heart cells enable the electrical impulse that causes them to contract and drives the heartbeat. Cellular ion concentrations were thought to be fairly constant, but scientists have now found that heart cells actually change their internal sodium and potassium levels during the day and night. This anticipates the daily demands of our life, allowing the heart to better adapt and support an increase heartbeat when we are active.

It is already known that there are daily clocks in heart cells and other tissues; normally synchronized by hormonal signals that align our internal daily rhythms with the day / night cycle. Daily rhythms of heart function have been known for years and are believed to be due to greater stimulation of the nervous system during the day. This new study, supported by the Medical Research Council and the AstraZeneca Blue Sky Initiative, shows that circadian rhythms within each heart cell can also affect heart rate.

The team, led by scientists at the MRC Laboratory for Molecular Biology in Cambridge, UK, working with AstraZeneca, say understanding how these changes in ion levels alter heart function throughout the day can help. explain why shiftworkers are more vulnerable to heart problems– because the ionic rhythms driven by the clocks of the heart are “out of sync” with their stimulation by the clocks of the brain. This new understanding could lead to better treatments and preventive measures to fight heart disease.

The study, published in the journal Nature Communication, discovered that these daily rhythms of sodium and potassium occur to enable changes in cellular proteins, with ions literally being pumped out to “make room” for daily increases in protein levels. Lead author of the study, Alessandra Stangherlin, was amazed to find that sodium / potassium levels vary by up to 30% in isolated cells and heart tissue. This gives a striking double daily variation to the electrical activity of isolated heart cells. In mice, this appears to be just as relevant to understanding daily changes in heart rate as nerve control.

Video illustrating the flow of ions in and out of heart cells and the corresponding changes in the concentration of certain proteins in the cell. Credit: Copyright MRC LMB

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

Although this study was conducted using cells and mice in the laboratory, its conclusions are supported by a recent study linked by collaborators, chaired by Professor David Bechtold of the University of Manchester. Their study demonstrated that circadian rhythms of heart rate and electrical activity are clearly evident in mice and humans, and that abrupt changes in behavioral routine or sleep patterns can disrupt these normal heart rhythms.

Taken together, these studies suggest that lifestyles that oppose our natural internal clock (such as shiftwork) can cause internal circadian rhythms within the body. heart cells to decouple from our behavior so that heart clocks no longer anticipate fluctuations in demand which, for most individuals, will be higher during the day. They suggest that this contributes to the increased risk of adverse events, such as arrhythmias and sudden cardiac death, when circadian rhythms are disturbed.

Dr John O’Neill said: “Many life-threatening heart problems occur at specific times of the day, and more often in shift workers. We believe that when the heart’s circadian clocks get out of sync with those in the brain, such as during shift work, our cardiovascular system may be less able to cope with the daily stresses of working life. This probably makes the heart more vulnerable to dysfunction. “

Peter Newham, Vice President, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, commented: “This collaboration is a wonderful example of why AstraZeneca is located in Cambridge, one of the most exciting hot spots in biosciences in the world. Having the MRC Molecular Biology Laboratory and John and Alessandro on our doorstep has really helped fuel this collaboration, bringing together our different perspectives and experiences to advance science.

Dr Megan Dowie, head of molecular and cellular medicine at the Medical Research Council, which funded the study, said: Scientific discovery. It addresses fundamental unanswered questions about how the body works and points to exciting new possibilities for therapeutic innovations.

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More information:
A. Stangherlin et al. The compensatory transport of ions buffers the daily rhythms of proteins to regulate the osmotic balance and cell physiology, Nature Communication (2021). DOI: 10.1038 / s41467-021-25942-4

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