What it takes to make a heartbeat

Do you know someone living with an abnormal heart rhythm? The latest data shows there’s a high chance that if you don’t personally experience cardiac arrhythmia in your own lifetime – someone close to you will.

Around 2.5 per cent of Australians are living with the worrying condition, which the Australian Bureau of Statistics says accounts for 3090 years of potential life lost in 2019 alone.

A person with a healthy heart will have a heart rate of between 60 and 100 beats per minute when resting. Arrhythmias occur when the electrical signals, which control your heartbeats, do not work properly and cause your heart to beat too fast, too slow or irregularly.

The Victor Chang Research Institute reports one in 10 Australians die suddenly due to an abnormal heart rhythm, which occurs most commonly just after a heart attack. But why?

My laboratory, in the School of Biomedical Sciences’ Department of Anatomy and Physiology, is investigating the early stages of heart development, seeking to identify novel genetic elements that may regulate cardiac development and function.

Our latest research, published in the Proceedings of National Academy of Sciences of the United States of America (PNAS), explains how we identified a gene required for cardiac rhythm – and how mutation or change of this gene causes cardiac arrhythmia, and eventual lethality. This helps us to understand the fundamentals of what it takes to make a heartbeat.

Until now, no-one has known what this gene does, which makes this research so exciting.

Interestingly, we were able to identify how the gene works by studying zebrafish which have complex beating hearts that operate in a similar way to human hearts.

In fact, 80 per cent of their genes are like ours.

Both use the same basic ‘equipment’, allowing researchers to figure out how a fish does it and take those lessons back to humans.

It was relatively easy to collect the eggs and study them using standard zebrafish breeding. As their eggs are translucent, we can watch the organs develop and function in the eggs by just putting them under a microscope.

After screening thousands of zebrafish families, we found one with inherited arrhythmia. Working backwards from there, we pinpointed a mutation in the gene known as tmem161b, that causes the condition.

It turned out to be a gene that was completely uncharacterised. In other words, until now no one has known what this gene does.

The big question is – will the finding only be relevant to fish, or is it also required for healthy cardiac rhythm in mammals?

To examine this, we introduced a mutation into a mouse and examined the effect on heart rhythm. We found that mice, too, had disrupted heart rhythm upon mutation of this gene.

Testing is underway but, given we see similar effects of this gene mutation on the heart in both fish and mice, it’s suspected this gene will also be important in how the human heart beats too.

Given the prevalence of cardiac arrhythmia in Australia, the more we know about how the heart works, the better.

The gene described in our research appears to play a fundamental function, so we expect it to be important in more than just controlling heart rhythm.

But that takes time to explore.

If all this turns out to be important in humans, it will provide a new candidate for genetic screening of patients with cardiac arrhythmia.

By studying thousands of individuals, we know that between 35 and 67 per cent of arrhythmias – depending on the nature of the disease – are inherited.

For these cases, diagnosis should be made using genetic screening. However, we cannot screen for mutations in genes if we don’t know those genes are involved in cardiac rhythm.

This discovery adds a new gene to the list of candidates that can be screened, which will assist in diagnosis and may also help to guide treatment.

This project also involved the University of Queensland, the Hubrecht Institute at Utrecht University, Amsterdam Medical Centre and The Florey Institute of Neuroscience and Mental Health.

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