A Calcium-Based Phantom Bursting Model for Pancreatic Islets
Richard Bertram, Arthur ShermanInsulin-secreting Beta-cells, located within the pancreatic islets of Langerhans, are excitable cells that produce regular bursts of action potentials when stimulated by glucose. This system has been the focus of mathematical investigation for two decades, spawning an array of mathematical models. Recently, a new class of models was introduced called ``phantom bursters" (Bertram et al., 2000), which accounts for the wide range of burst frequencies exhibited by islets via the interaction of more than one slow process. Here, we describe one implementation of the phantom bursting mechanism in which intracellular calcium controls the oscillations through both direct and indirect negative feedback pathways. We show how the model dynamics can be understood through an extension of the fast/slow analysis that is typically employed for bursting oscillations. From this perspective, the model makes use of multiple degrees of freedom to generate the full range of bursting oscillations exhibited by Beta-cells. The model also accounts for a wide range of experimental phenomena, including the ubiquitous triphasic response to the step elevation of glucose and responses to perturbations of internal calcium stores. Although not yet a complete model of all Beta-cell properties, it demonstrates the design principles that we anticipate will underlie future progress in Beta-cell modeling.