1. Numerical analysis of Ca2+ signaling in rat ventricular myocytes with realistic transverse-axial tubular geometry and inhibited sarcoplasmic reticulum.
- Author
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Cheng, Yuhui, Yu, Zeyun, Hoshijima, Masahiko, Holst, Michael J, McCulloch, Andrew D, McCammon, J Andrew, and Michailova, Anushka P
- Subjects
Sarcoplasmic Reticulum ,Cells ,Cultured ,Myocytes ,Cardiac ,Animals ,Rats ,Calmodulin ,Adenosine Triphosphate ,Imaging ,Three-Dimensional ,Computational Biology ,Calcium Signaling ,Algorithms ,Models ,Biological ,Computer Simulation ,Software ,Cells ,Cultured ,Imaging ,Three-Dimensional ,Models ,Biological ,Myocytes ,Cardiac ,Mathematical Sciences ,Biological Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
The t-tubules of mammalian ventricular myocytes are invaginations of the cell membrane that occur at each Z-line. These invaginations branch within the cell to form a complex network that allows rapid propagation of the electrical signal, and hence synchronous rise of intracellular calcium (Ca(2+)). To investigate how the t-tubule microanatomy and the distribution of membrane Ca(2+) flux affect cardiac excitation-contraction coupling we developed a 3-D continuum model of Ca(2+) signaling, buffering and diffusion in rat ventricular myocytes. The transverse-axial t-tubule geometry was derived from light microscopy structural data. To solve the nonlinear reaction-diffusion system we extended SMOL software tool (http://mccammon.ucsd.edu/smol/). The analysis suggests that the quantitative understanding of the Ca(2+) signaling requires more accurate knowledge of the t-tubule ultra-structure and Ca(2+) flux distribution along the sarcolemma. The results reveal the important role for mobile and stationary Ca(2+) buffers, including the Ca(2+) indicator dye. In agreement with experiment, in the presence of fluorescence dye and inhibited sarcoplasmic reticulum, the lack of detectible differences in the depolarization-evoked Ca(2+) transients was found when the Ca(2+) flux was heterogeneously distributed along the sarcolemma. In the absence of fluorescence dye, strongly non-uniform Ca(2+) signals are predicted. Even at modest elevation of Ca(2+), reached during Ca(2+) influx, large and steep Ca(2+) gradients are found in the narrow sub-sarcolemmal space. The model predicts that the branched t-tubule structure and changes in the normal Ca(2+) flux density along the cell membrane support initiation and propagation of Ca(2+) waves in rat myocytes.
- Published
- 2010