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Mapping the Heart’s Own Pacemaker in Mice

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In order to produce the heartbeats that keep you alive, the heart is dependent on electrical impulses. It is the job of a small congenital pacemaker, called the sinus node, to start the electrical signal of each heartbeat. The sinus node is invisible to the naked eye, but indispensable for the heart's contractions, which control the flow of blood through your body.

Researchers from the Department of Biomedical Sciences, the Novo Nordisk Foundation Center for Protein Research and the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen have now mapped the protein expression of the sinus node in mice. This means that they can now measure and analyse the proteins that make up the sinus node.

’We have measured and quantified 7,000 proteins in the sinus node itself and in the atrial tissue adjacent to the sinus node. We have compared the proteins between the two and in this way, we have been able to see exactly which proteins make the sinus node unique. Based on our data, we have established which proteins enables the sinus node to produce the electrical impulses behind each and every heartbeat’, says Alicia Lundby, Associate Professor at the Department of Biomedical Sciences.

The mapping of the proteins of the sinus node gives the researchers a deeper understanding of the fundamental structure of the heart. This knowledge may potentially be used for treatments that target heart diseases.

Many Surprises in the Heart

The researchers behind the study have spent several years developing the method that makes it possible to describe the protein expression in heart tissue biopsies. By using mass spectrometry, a method to analyse many proteins at the same time, the researchers have been able to go into great detail in the protein composition of the sinus node.

‘We already know a lot about the heart, but we also had many surprises. For example, in the protein profile of the sinus node, we could see that its muscle cells contain elements that enable them to contract. This is surprising, as the cells are not believed to use this function inside the sinus node. It tells us that the more we learn about the heart, the more doors we will open and make findings that we are not always prepared for’, says Alicia Lundby.

Better Understanding of Heart Diseases

‘The next step will be to focus on the human heart. We would like to do a mapping of the conduction system in the human heart. This is important in relation to heart diseases that involve an arrhythmia in the conduction system. If we do not know which proteins are expressed in this part of the heart, then we cannot find potential treatments for this part in the same efficient manner’, says Alicia Lundby.

Alicia Lundby believes that the investigation of the human conduction system may be completed as early as one year from now. The research team can reuse the method development, and in this way they already know exactly how to make the measurements and the analyses.

Reference: Linscheid et al. 2019. Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking. Nature Communications. DOI:https://doi.org/10.1038/s41467-019-10709-9.

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