Facial reconstruction

Search LJMU Research Online

Browse Repository | Browse E-Theses

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

Rajagopal, V and Bass, G and Walker, CG and Crossman, DJ and Petzer, A and Hickey, A and Siekmann, I and Hoshijima, M and Ellisman, MH and Crampin, EJ and Soeller, C (2015) Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes. PLoS Computational Biology, 11 (9). ISSN 1553-734X

[img]
Preview
Text
RajagopalEtAl_PLoSComputationalBiology2015.pdf - Published Version
Available under License Creative Commons Attribution.

Download (18MB) | Preview

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 literature ([Ca2+]i 1 μM; F/F0 5.5). However, our model predicted the variation in [Ca2+]i to be between 0.3 and 12.7 μM (~3 to 100 fold from resting value of 0.1 μM) and the corresponding F/F0 signal ranging from 3 to 9.5. We demonstrate in this study that: (i) heterogeneities in the [Ca2+]i transient are due not only to heterogeneous distribution and clustering of mitochondria; (ii) but also to heterogeneous local densities of RyR clusters. Further, we show that: (iii) these structureinduced heterogeneities in [Ca2+]i can appear in line scan data. Finally, using our unique method for generating RyR cluster distributions, we demonstrate the robustness in the [Ca2+]i transient to differences in RyR cluster distributions measured between rat and human cardiomyocytes.

Item Type: Article
Additional Information: Rajagopal V, Bass G, Walker CG, Crossman DJ, Petzer A, Hickey A, et al. (2015) Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes. PLoS Comput Biol 11(9): e1004417. https://doi.org/10.1371/journal.pcbi.1004417
Uncontrolled Keywords: 06 Biological Sciences, 08 Information And Computing Sciences, 01 Mathematical Sciences
Subjects: Q Science > QA Mathematics
Q Science > QH Natural history > QH301 Biology
Divisions: Applied Mathematics
Publisher: Public Library of Science (PLoS)
Related URLs:
Date Deposited: 21 Sep 2017 09:29
Last Modified: 21 Sep 2017 09:29
DOI or Identification number: 10.1371/journal.pcbi.1004417
URI: http://researchonline.ljmu.ac.uk/id/eprint/7136

Actions (login required)

View Item View Item