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J Struct Biol. 2014 Oct;188(1):55-60. doi: 10.1016/j.jsb.2014.08.005. Epub 2014 Aug 23.

Nanoscale three-dimensional imaging of the human myocyte.

Author information

1
Department of Biomedical Engineering, Washington University in St. Louis, MO, USA.
2
Department of Radiation Oncology, School of Medicine, Washington University in St. Louis, MO, USA.
3
FEI Company, Hillsboro, OR, USA.
4
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, MO, USA.
5
Department of Biomedical Engineering, Washington University in St. Louis, MO, USA. Electronic address: igor@wustl.edu.

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.

KEYWORDS:

Focused ion beam tomography; Metabolism; Myocyte; Ultrastructure

PMID:
25160725
PMCID:
PMC4295200
DOI:
10.1016/j.jsb.2014.08.005
[Indexed for MEDLINE]
Free PMC Article

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