Abstract
Objective. The transverse-axial tubule system (TATS) of cardiomyocytes allows a spatially coordinated conversion of electrical excitation into an intracellular Ca2+ signal and consequently contraction. Previous reports have indicated alterations of structure and/or volume of the TATS in cardiac hypertrophy and failure, suggesting a contribution to the impairment of excitation contraction coupling. To test whether structural alterations are present in human heart failure, the TATS was visualized in myocytes from failing and non-failing human hearts. Methods and Results. In freshly isolated myocytes, the plasmalemmal membranes were labeled with Di-8-ANEPPS and imaged using two-photon excitation at 780 nm. Optical sections were taken every 300 nm through the cells. After deconvolution, the TATS was determined within the 3D data sets, revealing no significant difference in normalized surface area or volume. To rule out possible inhomogeneity in the arrangement of the TATS, Euclidian distance maps were plotted for every section, allowing to measure the closest distance between any cytosolic and any membrane point. There was a trend towards greater spacing in cells from failing hearts, without statistical significance. Conclusion. Only small changes, but no significant changes in the geometrical dimensions of the TATS were observed in cardiomyocytes from failing compared to non-failing human myocardium.
Highlights
Regular cardiac function is dependent on coordinated contraction of all myocytes forming the heart
To test whether structural alterations are present in human heart failure, the transverse-axial tubule system (TATS) was visualized in myocytes from failing and non-failing human hearts
Since intercellular coordination is achieved by propagated electrical excitation and myofilament activation is calcium-dependent, contraction of the individual myocyte critically depends on a homogenous transduction of the action potential into an intracellular calcium signal
Summary
Regular cardiac function is dependent on coordinated contraction of all myocytes forming the heart. Since intercellular coordination is achieved by propagated electrical excitation and myofilament activation is calcium-dependent, contraction of the individual myocyte critically depends on a homogenous transduction of the action potential into an intracellular calcium signal. This first step of cardiac excitation contraction coupling (ECC) is mediated by voltage-dependent calcium channels embedded in the sarcolemma. The distinct geometrical arrangement of the cell membrane provides the important spatial relationship of key proteins of ECC, for example, positioning of the L-type Ca-channels approximately 12 nm opposite of SR calcium release channels [2]
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