Desmin is essential for the structure and function of the sinoatrial node: implications for increased arrhythmogenesis

Our objective was to investigate the effect of desmin depletion on the structure and function of the sinoatrial pacemaker complex (SANcl) and its implication in arrhythmogenesis. Analysis of mice and humans (SANcl) indicated that the sinoatrial node exhibits high amounts of desmin, desmoplakin, N-cadherin, and β-catenin in structures we call “lateral intercalated disks” connecting myocytes side by side. Examination of the SANcl from an arrhythmogenic cardiomyopathy model, desmin-deficient (Des-/-) mouse, by immunofluorescence, ultrastructural, and Western blot analysis showed that the number of these lateral intercalated disks was diminished. Also, electrophysiological recordings of the isolated compact sinoatrial node revealed increased pacemaker systolic potential and higher diastolic depolarization rate compared with wild-type mice. Prolonged interatrial conduction expressed as a longer P wave duration was also observed in Des-/mice. Upregulation of mRNA levels of both T-type Ca2+ current channels, Cav3.1 and Cav3.2, in the Des-/- myocardium (1.8- and 2.3-fold, respectively) and a 1.9-fold reduction of funny hyperpolarization-activated cyclic nucleotide-gated K+ channel 1 could underlie these functional differences. To investigate arrhythmogenicity, electrocardiographic analysis of Des-deficient mice revealed a major increase in supraventricular and ventricular ectopic beats compared with wild-type mice. Heart rate variability analysis indicated a sympathetic predominance in Des-/- mice, which may further contribute to arrhythmogenicity. In conclusion, our results indicate that desmin elimination leads to structural and functional abnormalities of the SANcl. These alterations may be enhanced by the sympathetic component of the cardiac autonomic nervous system, which is predominant in the desmin-deficient heart, thus leading to increased arrhythmogenesis. Copyright © 2020 the American Physiological Societ

The challenging paradigm of interrelated energy systems towards a more sustainable future

This paper brings together several contemporary topics in energy systems aiming to provide a literature review based reflection on how several interrelated energy systems can contribute together to a more sustainable world. Some directions are discussed, such as the improvement of the energy efficiency and environmental performance of systems, the development of new technologies, the increase of the use of renewable energy sources, the promotion of holistic and multidisciplinary studies, and the implementation of new management rules and "eco-friendly and sustainable" oriented policies at different scales. The interrelations of the diverse energy systems are also discussed in order to address their main social, economic and environmental impacts. The subjects covered include the assessment of the electricity market and its main players (demand, supply, distribution), the evaluation of urban systems (buildings, transportation, commuting), the analysis of the implementation of renewable energy cooperatives, the discussion of the diffusion of the electric vehicle and the importance of new bioenergy systems. This paper also presents relevant research carried out in the framework of the Energy for Sustainability (EfS) Initiative of the University of Coimbra, linking the reviewed areas to the multidisciplinary approach adopted by the EfS Initiative. To conclude, several research topics that should be addressed in the near future are proposed