Subcellular Structural Changes in Diabetic Cardiomyopathy and its Impact on Cardiac Cell Calcium Dynamics

Diabetic cardiomyopathy is characterized by reduced cardiac output and is linked to subcellular level changes in cell structure and function. Although a number of studies have quantified the effect on protein distribution, Ca2+ handling and kinetics, the alterations in spatial organization of the major cell organelles have not been fully quantified before. We therefore studied organelle distribution in detail to study the effect of changes on, for example, calcium dynamics in an integrated manner. Cells from healthy and diabetic (following injection of STZ) Wistar rats were imaged under a transmission electron microscope. The spatial distribution of the mitochondria and myofibrils were analyzed in these images to determine a statistical model (using spatial statistics theory) that would adequately represent their characteristic distribution in cells from healthy versus diabetic animals. The model was calibrated using control and diabetic animal data such as shown in Fig. 1. This also allowed us to statistically quantify the differences in spatial organization. We present these structural differences and assess the influence of these changes on the spatial and temporal dynamics of cytosolic calcium during calcium-induced calcium release in an integrated 3D computational model.View Large Image | View Hi-Res Image | Download PowerPoint Slide