期刊
JOURNAL OF CELL SCIENCE
卷 122, 期 7, 页码 1005-1013出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.028175
关键词
Ca2+ channel; Cardiac muscle; Electron microscopy; Excitation-contraction coupling; Membrane-bound organelle; Mitochondria
类别
资金
- National Institutes of Health [P41 RR004050, P41 RR008605]
- The American Heart Association
- Uehara Memorial Foundation
- Banyu Life Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Mathematical Sciences [0821816] Funding Source: National Science Foundation
In the current study, the three-dimensional (3D) topologies of dyadic clefts and associated membrane organelles were mapped in mouse ventricular myocardium using electron tomography. The morphological details and the distribution of membrane systems, including transverse tubules (T-tubules), junctional sarcoplasmic reticulum (SR) and vicinal mitochondria, were determined and presumed to be crucial for controlling cardiac Ca2+ dynamics. The geometric complexity of T- tubules that varied in diameter with frequent branching was clarified. Dyadic clefts were intricately shaped and remarkably small (average 4.39 X 10(5) nm(3), median 2.81 X 10(5) nm(3)). Although a dyadic cleft of average size could hold maximum 43 ryanodine receptor (RyR) tetramers, more than one-third of clefts were smaller than the size that is able to package as many as 15 RyR tetramers. The dyadic clefts were also adjacent to one another (average end-to-end distance to the nearest dyadic cleft, 19.9 nm) and were distributed irregularly along T-tubule branches. Electron-dense structures that linked membrane organelles were frequently observed between mitochondrial outer membranes and SR or T-tubules. We, thus, propose that the topology of dyadic clefts and the neighboring cellular micro-architecture are the major determinants of the local control of Ca2+ in the heart, including the establishment of the quantal nature of SR Ca2+ releases (e.g. Ca2+ sparks).
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