title: Mechanical modulation of the transverse tubular system of ventricular cardiomyocytes.
abstract: 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.
authors.affiliation: Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112-5000, USA. mcnary@cvrti.utah.edu
authors.forename: Thomas G
authors.initials: TG
authors.lastname: McNary
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Spitzer
authors.forename: Hilary
authors.initials: H
authors.lastname: Holloway
authors.forename: John H B
authors.initials: JH
authors.lastname: Bridge
authors.forename: Peter
authors.initials: P
authors.lastname: Kohl
authors.forename: Frank B
authors.initials: FB
authors.lastname: Sachse
mesh_terms: D000185:Actinin / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D002470:Cell Survival; D003599:Cytoskeleton / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology*; D055595:Mechanical Phenomena; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D012518:Sarcomeres / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D000185:Actinin