Calcium Oscillations and Waves Generated by Multiple Release Mechanisms in Pancreatic Acinar Cells

Abstract

We explore the dynamic behavior of a model of calcium oscillations and wave propagation in the basal region of pancreatic acinar cells [Sneyd, J., et al., Biophys. J. 85: 1392-1405, 2003]. Since it is known that two principal calcium release pathways are involved, inositol trisphosphate receptors (IPR) and ryanodine receptors (RyR), we study how the model behavior depends on the density of each receptor type. Calcium oscillations can be mediated either by IPR or RyR. Continuous increases in either RyR or IPR density can lead to the appearance and disappearance of oscillations multiple times, and the two receptor types interact via their common effect on cytoplasmic calcium concentration and the subsequent effect on the total amount of calcium inside the cell. Increases in agonist concentration can stimulate oscillations via the RyR by increasing calcium influx. Using a two time-scale approach, we explain these complex behaviors by treating the total amount of cellular calcium as a slow parameter. Oscillations are controlled by the shape of the slow manifold and where it intersects the nullcline of the slow variable. When calcium diffusion is included, the existence of traveling waves in the model equation is strongly dependent on the interplay between the total amount of calcium in the cell and membrane transport, a feature that can be experimentally tested. Our results help us understand the behavior of a model that includes both receptors in comparison to the properties of each receptor type in isolation.