Mathematical Modeling Demonstrates How Multiple Slow Processes Can Provide Adjustable Control of Islet Bursting

Margaret Watts, Joel Tabak, Richard Bertram

Pancreatic islets exhibit bursting oscillations that give rise to oscillatory Calcium entry and insulin secretion from beta-cells. These oscillations are driven by a slowly activating potassium current, Kslow, which is composed of two components: an ATP-sensitive potassium current and a CalciuM-activated potassium current thr ough SK4 channels. Using a mathematical model of pancreatic beta-cells, we analyze how the factors that comprise Kslow can contribute to bursting. We employ the dominance factor technique developed recently to do this and demonstrate that the contributions t hat the slow processes make to bursting are non-obvious and often counter-intuitive, and that their contributions vary with parameter values and are thus adjustable.