Journal
DEVELOPMENTAL BIOLOGY
Volume 239, Issue 2, Pages 204-214Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/dbio.2001.0437
Keywords
development; excitation-contraction coupling; Ca2+ release unit; ryanodine receptor; sarcoplasmic reticulum; skeletal muscle; transverse tubules
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Funding
- NIAMS NIH HHS [P01 AR 44650] Funding Source: Medline
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Skeletal muscle Ca2+ release units (CRUs) are junctions of the surface membrane/T-tubule system and the sarcoplasmic reticulum (SR) that function in excitation-contraction coupling. They contain high concentrations of dihydropyridine receptors (DHPRs) in the T-tubules and of ryanodine receptors (RyR) in the SR and they are positioned at specific locations in the sarcomere. In order to characterize the sequence of developmental steps leading to the specific molecular and structural organization of CRUs, we applied a range of imaging techniques that allowed us to follow the differentiation of the membrane compartments and the expression of junctional proteins in developing mouse diaphragm muscle. We find that docking of the two membrane systems precedes the incorporation of the RyRs into the junctions, and that T-tubule/SR junctions are formed and positioned at the I-A interface at a stage when the orientation of T-tubule is predominantly longitudinal. Thus, the sequence of developmental events is first the docking of T-tubules and SR, secondly the incorporation of RyR in the junctions, thirdly the positioning of the junctions in the sarcomere, and only much later the transverse orientation of the T-tubules. These sequential stages suggests an order of inductive processes for the molecular differentiation and structural organization of the CRUs in skeletal muscle development. (C) 2001 Academic Press.
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