Mechanical modulation of the transverse tubular system of ventricular cardiomyocytes

• Published in: Progress in biophysics and molecular biology Vol. 110; no. 2-3; pp. 218 - 225
• Main Authors: McNary, Thomas G., Spitzer, Kenneth W., Holloway, Hilary, Bridge, John H.B., Kohl, Peter, Sachse, Frank B.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2012
• Subjects: Actinin - metabolism; Animals; Biomechanical Phenomena; Cell Survival; Confocal microscopy; Contraction; Cytoskeleton - metabolism; Heart Ventricles - cytology; Mechanical Phenomena; Myocyte; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Rabbits; Sarcomeres - metabolism; Strain; Stress, Mechanical; Transverse tubule; PBS; WGA; t-system; t-tubule; Confocal microscopy; SL; Transverse tubule; TEM; Contraction; Myocyte; Strain; RyRs
• ISSN: 0079-6107; 1873-1732
• DOI: 10.1016/j.pbiomolbio.2012.07.010

In most mammalian cardiomyocytes, the transverse tubular system (t-system) is a major site for electrical signaling and excitation–contraction coupling. The t-system consists of membrane invaginations, which are decorated with various proteins involved in excitation–contraction coupling and mechano-electric feedback. Remodeling of the t-system has been reported for cells in culture and various types of heart disease. In this paper, we provide insights into effects of mechanical strain on the t-system in rabbit left ventricular myocytes. Based on fluorescent labeling, three-dimensional scanning confocal microscopy, and digital image analysis, we studied living and fixed isolated cells in different strain conditions. We extracted geometric features of transverse tubules (t-tubules) and characterized their arrangement with respect to the Z-disk. In addition, we studied the t-system in cells from hearts fixed either at zero left ventricular pressure (slack), at 30 mmHg (volume overload), or during lithium-induced contracture, using transmission electron microscopy. Two-dimensional image analysis was used to extract features of t-tubule cross-sections. Our analyses of confocal microscopic images showed that contracture at the cellular level causes deformation of the t-system, increasing the length and volume of t-tubules, and altering their cross-sectional shape. TEM data reconfirmed the presence of mechanically induced changes in t-tubular cross sections. In summary, our studies suggest that passive longitudinal stretching and active contraction of ventricular cardiomyocytes affect the geometry of t-tubules. This confirms that mechanical changes at cellular levels could promote alterations in partial volumes that would support a convection-assisted mode of exchange between the t-system content and extracellular space.