Abstract
In cardiomyocytes, coordinated calcium release from intracellular stores through ryanodine receptor (RyR) clusters is key to contraction. Recently, a deconvolution algorithm (CaCLEAN) was proposed to detect the functional response of RyR clusters from confocal imaging of live cells. However, CaCLEAN cluster detection remained unvalidated without ground truth values. We developed a structurally realistic computational model of calcium emanating from RyR clusters in a rat ventricular cardiomyocyte during the first 30 ms of the calcium transient. The effects of RyR cluster density and mitochondria acting as diffusion barriers were examined. Confocal microscopy images were simulated and analysed using CaCLEAN. CaCLEAN detection accuracy was more sensitive to RyR cluster density than the presence of mitochondria. Detection recall and precision varied between 0.69 and 0.82 in densely and sparsely-packed RyR cluster distribution cases, respectively. This sensitivity to cluster packing also affected the distance from the imaging plane clusters were detected.