Mathematical modeling demonstrates how multiple slow processes can provide adjustable control of islet bursting

摘要

Pancreatic islets exhibit bursting oscillations that give rise to oscillatory Ca²⁺ entry and insulin secretion from β-cells. These oscillations are driven by a slowly activating K⁺ current, Kslow, which is composed of two components: an ATP-sensitive K⁺ current and a Ca²⁺-activated K⁺ current through SK4 channels. Using a mathematical model of pancreatic β-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 that 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.