Methylation of Na+ channels in cardiac cells - the mechanism behind sudden death

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Sudden cardiac death kills approximately 40,000 young (<50 years of age) people every year in Europe. Genetic analyses can explain the majority of these cases, but not all. We are interested in post-translational modifications (PTMs) of cardiac proteins and their role in cardiac and cardiovascular disease, including sudden cardiac death in the young. Arginine methylation is one such PTM and we have investigated methylation of sodium channels, troponins,  and other proteins that are essential to cardiac excitation and contraction [1,2]. 

Despite all these efforts, we are still far from understanding the biological basis of many sudden cardiac death syndromes. Synergistic investigations that bridge biology and mathematics can provide unique mechanistic insights into these important public health issues. The motivation behind this video was to inspire young scientists in-the-making to become engaged with the breadth of science, where hope can still find a place.

Video by Pedro Beltran-Alvarez (Biomedical Sciences, University of Hull, UK), and Carlos Beltran and Irene Olmo (TEAMCO, University of Cantabria, Spain).

References

1. Beltran-Alvarez, Pedro, Espejo, Alexsandra, Schmauder, Ralf, Beltran, Carlos, Mrowka, Ralf, Linke, Thomas, Batlle, Montserrat, Pérez-Villa, Félix, Pérez, Guillermo J., Scornik, Fabiana S., Benndorf, Klaus, Pagans, Sara, Zimmer, Thomas and Brugada, Ramon(2013), Protein arginine methyl transferases-3 and -5 increase cell surface expression of cardiac sodium channel, FEBS Letters, 587, doi: 10.1016/j.febslet.2013.07.043

2. Onwuli DO, Samuel SF, Sfyri P, Welham K, Goddard M, Abu-Omar Y, Loubani M, Rivero F, Matsakas A, Benoit DM, Wade M, Greenman J, Beltran-Alvarez P. (2019) The inhibitory subunit of cardiac troponin (cTnl) is modified by arginine methylation in the human heartInt J Cardiol. 282:76-80. doi: 10.1016/j.ijcard.2019.01.102.

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