Heart cell connections could predict rhythm disorders in the future

In a research article published online in Nature Communications last January 20, hearts suffering from disease may be disrupted from their normal rhythm because of structural differences, which are visible for the first time, in the protein groups that are seen to connect muscle cells of the heart.

Using powerful imaging techniques and mathematical models, researchers from the NYU Langone Medical Center were able to reconstruct, for the first time, 3D images of structures called intercalated discs, which are proteins that actually connect heart muscle cells. These proteins are also responsible for passing electrical signals and the pumping force that the heart needs in order to function properly.

The research was able to show that these intercalated discs occur together in clusters, and in cases where these proteins are farther apart than normal, even by a distance as small as a billionth of a meter, electrical malfunctions may occur.

Senior study investigator Mario Delmar, MD, PhD, the Patricia and Robert Martinsen Professor of Cardiology in the Department of Medicine's Leon H. Charney Division of Cardiology at NYU Langone, says that Our new images could someday help physicians and genetic counsellors more accurately identify people at risk before they develop potentially life-threatening arrhythmias, electric disorders that throw off the heart's rhythm. Dr. Delmar's long term-goal is to be able to devise a blood test that will be able to detect dangerous disc protein structures as a component of mass screening.

Cadherins

Previous researches have shown that these intercalated discs are usually composed of cadherins, which are a class of proteins that anchor one cell on to another so that they could pass on a combined pumping force, which is called adhesion. Located within the discs are also protein channels that when stimulated with the proper signal, allow sodium ions to flow inside, thereby triggering heart muscle cell contraction. This is known as excitability.

It was previously those that adhesion and excitability were performed by different proteins, but the present study shows that they actually work together. Delmar and colleagues were able to identify the existence in the discs of distinct clusters of both the adhesion protein N-cadherin, and another protein, Nav 1.5, which is related to sodium ion channels.

These two clusters that were identified are speculated to be sites of crosstalk between contractile and electrical functions in heart muscle cells. The most important finding perhaps is that their discovery of the distance between adhesion and excitability complexes may actually provide a new way to measure risk of some diseases through imaging. This is especially applicable in diseases where genetic mutations can be related to differences in protein spacing.

According to their results, around 60 percent of N-cadherin in the intercalated discs of mice used in the study were clustered within a proximity of 100 nanometers from Nav 1.5. Images of the proteins showed that they were quite highly organized. The researchers speculate that the closeness of the proteins might be essential to coordinating the electrical properties of the heartbeat.