Abstract
Electrical activity in pancreatic beta-cells plays a pivotal role in glucose-stimulated insulin secretion by coupling metabolism to calcium-triggered exocytosis. Mathematical models based on rodent data have helped in understanding the mechanisms underlying the electrophysiological patterns observed in laboratory animals. However, human beta-cells differ in several aspects, and in particular in their electrophysiological characteristics, from rodent beta-cells. Hence, from a clinical perspective and to obtain insight into the defects in insulin secretion relevant for diabetes mellitus, it is important to study human beta-cells.To investigate the role of small conductance calcium-activated potassium SK-channels, we build on a recently developed mathematical model of electrical activity based entirely on detailed ion channel characteristics of human beta-cells.We show that the inclusion of SK-channels allows us to investigate various patterns of electrical activity, and interpret atypical and non-intuitive responses to ion channel blockers in human beta-cells. However, our simulations suggest that the effect on electrical activity of SK channel antagonists is minimal. This is supported by preliminary experimental data.
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