Importance of cell variability for calcium signaling in rat airway myocytes

Calcium signaling controls several essential physiological functions in different cell types. Hence, it is not surprising that different aspects of Ca(2+) dynamics are in the focus of in-depth and extensive investigations. Efforts concentrate on the development of proper theoretical models that would provide a unified description of Ca(2+) signaling. Remarkably, experimentally recorded Ca(2+) signals exhibit a rather large diversity, which can be observed irrespective of the cell type, measuring techniques, or the nature of the signal. Our goal in the present study therefore is to present a theoretical explanation for the variability observed in experiments, whereby we focus on caffeine-induced Ca(2+) responses in isolated airway myocytes. By employing a stochastic model, we first test whether the observed variability can be attributed to intrinsic fluctuations that are a common feature of biochemical reactions that govern Ca(2+) signalization. We find that stochastic effects, within ranges that correspond to actual conditions in the cell, are far too modest to explain the large diversity observed in experimental data. Foremost, we reveal that only cell variability in theoretical modeling can appropriately describe the observed diversity in single-cell responses.