. bi o - ph ] 8 S ep 2 00 5 Role of mitochondria and network connectivity in intercellular calcium oscillations

Mitochondria are large-scale regulators of cytosolic calcium (Ca 2+) under normal cellular conditions. In this paper we model the complex behavior of mitochondrial calcium during the action of inositol 1,4,5-trisphosphate (IP3) on a single cell and find results that are in good agreement with recent experimental studies. We also study the influence of the cellular network connectivity on intercellular signalling via gap junction diffusion. We include in our model the dependence of the junctional conductivity on the cytosolic calcium concentrations in adjacent cells. We consider three different mechanisms of calcium wave propagation through gap junctions: via Ca 2+ diffusion, IP3 diffusion, and both Ca 2+ and IP3 diffusion. We show that IP3 diffusion is the mechanism of Ca 2+ wave propagation and that Ca 2+ diffusion is the mechanism of synchronization of cytosolic Ca 2+ oscillations in adjacent cells. We also study the role of different topological configurations of cellular connectivity on these phenomena and show that within the context of the model different topolog-ical structures play an important role in calcium wave propagation.