Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes

PLoS Computational Biology
Vijay RajagopalChristian Soeller

Abstract

Spatio-temporal dynamics of intracellular calcium, [Ca2+]i, regulate the contractile function of cardiac muscle cells. Measuring [Ca2+]i flux is central to the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease. However, current imaging techniques are limited in the spatial resolution to which changes in [Ca2+]i can be detected. Using spatial point process statistics techniques we developed a novel method to simulate the spatial distribution of RyR clusters, which act as the major mediators of contractile Ca2+ release, upon a physiologically-realistic cellular landscape composed of tightly-packed mitochondria and myofibrils. We applied this method to computationally combine confocal-scale (~ 200 nm) data of RyR clusters with 3D electron microscopy data (~ 30 nm) of myofibrils and mitochondria, both collected from adult rat left ventricular myocytes. Using this hybrid-scale spatial model, we simulated reaction-diffusion of [Ca2+]i during the rising phase of the transient (first 30 ms after initiation). At 30 ms, the average peak of the simulated [Ca2+]i transient and of the simulated fluorescence intensity signal, F/F0, reached values similar to that found in the lite...Continue Reading

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May 24, 2016·Progress in Biophysics and Molecular Biology·Eva A Rog-ZielinskaPeter Kohl
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Methods Mentioned

BETA
electron microscopy
electron
confocal microscopy
light diffraction
confocal
electron tomography
structural microscopy

Software Mentioned

TetGen
CellML
PYME
- Microscopy Environment ( PYME
PYthon
MATLAB
simulator
iso2mesh
IMOD
OpenCMISS

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