The phantom burster model for pancreatic beta-cells

Pancreatic beta -cells exhibit bursting oscillations with a wide range of p eriods. Whereas periods in isolated cells are generally either a few second s or a few minutes, in intact islets of Langerhans they are intermediate (1 0-60 s). We develop a mathematical model for beta -cell electrical activity capable of generating this wide range of bursting oscillations. Unlike pre vious models, bursting is driven by the interaction of two slow processes, one with a relatively small time constant (16 s) and the other with a much larger time constant (1-2 min). Bursting on the intermediate time scale is generated without need for a slow process having an intermediate time const ant, hence phantom bursting. The model suggests that isolated cells exhibit ing a fast pattern may nonetheless possess slower processes that can be bro ught out by injecting suitable exogenous currents. Guided by this, we devis e an experimental protocol using the dynamic clamp technique that reliably elicits islet-like, medium period oscillations from isolated cells. Finally , we show that strong electrical coupling between a fast burster and a slow burster can produce synchronized medium bursting, suggesting that islets m ay be composed of cells that are intrinsically either fast or slow, with fe w or none that are intrinsically medium.