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Biophys. J. BioFAST: First Published April 7, 2006. doi:10.1529/biophysj.105.077180
© 2006 by the Biophysical Society.


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BIOPHYSICAL THEORY AND MODELING

Three-Dimensional Distribution of Ryanodine Receptor Clusters in Cardiac Myocytes

Ye Chen-Izu 1, Stacey L McCulle 1, Chris W Ward 2, Christian Soeller 3, Bryan M Allen 4, Cal Rabang 5, Mark B Cannell 3, C William Balke 1 and Leighton T Izu 1*

1 University of Kentucky
2 University of Maryland Baltimore
3 Auckland University
4 Rochester Institute of Technology
5 University of Maryland at Baltimore County

* To whom correspondence should be addressed. E-mail: leightonizu{at}uky.edu.

Submitted on November 3, 2005
Revised on December 2, 2005
Accepted on 1 February 2006


   Abstract
The clustering of ryanodine receptors (RyR2) into functional Ca2+ release units is central to current models for cardiac excitation-contraction (E-C) coupling. Using immunolabeling and confocal microscopy, we have analyzed the distribution of RyR2 clusters in rat atrial and ventricular myocytes. The resolution of the 3-D structure was improved by a novel transverse sectioning method as well as digital deconvolution. In contrast to earlier reports, the mean RyR2 cluster transverse spacing was measured 1.05 µm in ventricular myocytes and estimated 0.97 µm in atrial myocytes. Intercalated RyR2 clusters were found interspersed between the Z-disks on the cell periphery but absent in the interior, forming double rows flanking the local Z-disks on the surface. The longitudinal spacing between the adjacent rows of RyR2 clusters on the Z-disks was measured to have a mean value of 1.87 µm in ventricular and 1.69 µm in atrial myocytes. The measured RyR2 cluster distribution is compatible with models of Ca2+ wave generation. The size of the typical RyR2 cluster was close to 250 nm, and this suggests that about 100 RyR2s might be present in a cluster. The importance of cluster size and 3-D spacing for current E-C coupling models is discussed.

Key Words: atrial myocyte, calcium signaling, calcium sparks, excitation-contraction coupling, ventricular myocyte




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Copyright © 2006 by the Biophysical Society.