Clin Res Cardiol (2021). 10.1007/s00392-021-01933-9

Confocal Microscopy-Based Characterisation of the Tubular System in Cardiomyocytes
F. Sonak1, J. Greiner1, T. Kok1, P. Kohl1, E. Rog-Zielinska1
1Institut für Experimentelle Kardiovaskuläre Medizin, Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH, Freiburg im Breisgau;

The beating of the heart is governed by the coordinated activity of contractile muscle cells -- cardiomyocytes (CM). Each CM contains an elaborate network of regular deep surface membrane invaginations (TATS). TATS is an essential link between the excitation and contraction of individual CM, and in consequence -- the whole heart. The  TATS network is usually characterised by a high degree of complexity, and any changes to the network morphology can be detrimental to cardiac function.

Basic research into cardiac health and disease relies on the use of animal models, allowing researchers to develop safe and effective pharmaceutical, genetic, environmental, and surgical approaches to address various cardiac pathologies. However, successful translation of animal model-based findings into clinics is hindered by the inherent  differences in cardiac structure and function between species, making careful identification of the most appropriate study model essential. TATS structure has been previously shown to differ between most commonly used laboratory species and humans, no quantitative analysis however has been performed to date. Here, a workflow was developed for preparation, imaging, and near-fully automated three dimensional analysis of TATS in several species -- African clawed frog, rabbit, pig, and cow.

Quantitative analysis was performed to determine the density, connectivity, and orientations of TATS elements. Among all species studied, rabbit CM were shown to exhibit higher TATS density, and connectivity when compared to pig. No TATS could be identified in frog tissue.

In the future, a more extensive analysis should be performed, including additional commonly used laboratory species (e.g. mouse), as well as human. Furthermore, detailed quantitative analysis of TATS across species might make it possible to correlate the morphological TATS parameters with other physiological characteristics such as heart size, CM size, or beating rate -- potentially providing novel insights regarding TATS relevance in supporting cardiac function.


https://dgk.org/kongress_programme/ht2021/BS946.htm