Nanoscale three-dimensional imaging of the human myocyte.

Abstract

The ventricular human myocyte is spatially organized for optimal ATP and Ca(2+) delivery to sarcomeric myosin and ionic pumps during every excitation-contraction cycle. Comprehension of three-dimensional geometry of the tightly packed ultrastructure has been derived from discontinuous two-dimensional images, but has never been precisely reconstructed or analyzed in human myocardium. Using a focused ion beam scanning electron microscope, we created nanoscale resolution serial images to quantify the three-dimensional ultrastructure of a human left ventricular myocyte. Transverse tubules (t-tubule), lipid droplets, A-bands, and mitochondria occupy 1.8, 1.9, 10.8, and 27.9% of the myocyte volume, respectively. The complex t-tubule system has a small tortuosity (1.04±0.01), and is composed of long transverse segments with diameters of 317±24nm and short branches. Our data indicates that lipid droplets located well beneath the sarcolemma are proximal to t-tubules, where 59% (13 of 22) of lipid droplet centroids are within 0.50μm of a t-tubule. This spatial association could have an important implication in the development and treatment of heart failure because it connects two independently known pathophysiological alterations, a substrate switch from fatty acids to glucose and t-tubular derangement.

DOI: 10.1016/j.jsb.2014.08.005

Cite this paper

@article{Sulkin2014NanoscaleTI, title={Nanoscale three-dimensional imaging of the human myocyte.}, author={Matthew S Sulkin and Fei Yang and Katherine M Holzem and Brandon Van Leer and Cliff Bugge and Jacob I Laughner and Karen Green and Igor R Efimov}, journal={Journal of structural biology}, year={2014}, volume={188 1}, pages={55-60} }