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Cutting-Edge imaging unravels sex-specific structural variations in the heart!

Photo: Gordon Johnson from Pixabay.

The hearts of men and women have remarkable differences in terms of their function in health and which heart diseases impact them. In particular, there is a major difference between prevalent heart failure types experienced by men and women. Sex-specific approaches are very much needed to handle heart failure, and we are at the stage where there are many gaps in our knowledge related to it.

A recent study published in Journal of Physiology by the Laboratory of Systems Biology from TalTech (Tallinn, Estonia) with the collaboration of a group from Oslo University Hospital (Oslo, Norway) explores the unique traits of heart cells in men and women. For that, it employs cutting-edge microscopy techniques to explore the structural and functional disparities in the cardiomyocytes of male and female mice. Particularly, the researchers focus on the beat-to-beat calcium signals to uncover pivotal distinctions that may reshape our perspective on sex-specific heart physiology. The research was supported by Estonian Research Council grant PRG1127.

The heart is an unique organ which cannot take a break and rest. For its function, it combines electrical stimulation, biochemical signaling and reactions, with mechanical work. In this research, the groups looked into a link between electrical and biochemical signaling used in the heart in a single muscle cell. That biochemical signal is carried by calcium which triggers mechanical work. Most previous studies on sex differences in heart physiology suggest that male hearts display larger swings in calcium concentration due to higher number calcium releases from RyR (calcium sparks) and heightened stress responses during adrenergic stimulation.


There are many intracellular structures that make this transition possible from electrical to chemical signal. Those include specialized membrane structures (t-tubules) and calcium release channels (RyRs).  In this project, the scientists focused on important calcium signaling related intracellular structural elements, how their arrangement is different between sexes, and whether it impacts the cardiac calcium signaling.

This study reveals unexpected subtleties. In contrast to the earlier studies, this study shows that female heart cells showcase a higher frequency of elementary calcium release events – calcium sparks. The difference with the earlier studies is probably caused by better conditioning of the cells before measurements. Leveraging cutting microscopy imaging techniques and advanced image analysis, the differences in calcium spark frequencies between female and male cardiac muscle cells are attributed to the differences in the arrangement of RyRs in female hearts. At the same time, there are differences in the arrangement of the t-tubular network between female and male cardiomyocytes.

The figure shows the arrangement of calcium channels (RyR) in the cardiomyocytes of female and male animals. Author: TalTech

However, delving further into the overall behavior of heart cells, the study identifies similar patterns in calcium concentration swings between men and women. Thus, these differences are balanced in intact cells, resulting in similar calcium signaling in electrically stimulated male and female cardiomyocytes. Nevertheless, the nuanced structural variations uncovered, coupled with the precision of advanced imaging, suggest potential insights into how heart pathologies may manifest differently in males and females. Based on these promising results, these advanced imaging techniques are further developed as a part of Estonian Research Council project PSG832 which looks into the details of calcium signaling in the heart at nanoscale.

In summary, the study shed light on the subtle variations in how calcium is handled in male and female hearts. This not only deepens our understanding but also opens promising avenues for personalized sex-specific approaches to heart treatments.

This article is brought to you by prof. Marko Vendelin and prof. Martin Laasmaa, originally published on the Tallinn University of Technology webpage. The published paper discussed in this article is available at

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