Phantom bursting may underlie electrical bursting in single pancreatic [formula omitted]-cells

Abstract

Insulin is secreted by pancreatic β-cellsthat are electrically coupled into micro-organs called islets of Langerhans. The secretion is due to the influx of Ca2+ions that accompany electrical impulses, which are clustered into bursts. So-called “medium bursting” occurs in many β-cellsin intact islets, while in other islets the β-cellsexhibit “slow bursting”, with a much longer period. Each burst brings in Ca2+ that, through exocytosis, results in insulin secretion. When isolated from an islet, β-cellsbehave very differently. The electrical activity is much noisier, and consists primarily of trains of irregularly-timed spikes, or fast or slow bursting. Medium bursting, so often seen in intact islets, is rarely if ever observed. In this study, we examine what the isolated cell behavior can tell us about the mechanism for bursting in intact islets. A previous mathematical study concluded that the slow bursting observed in isolated β-cells, and therefore most likely in islets, must be due to intrinsic glycolytic oscillations, since this mechanism for bursting is robust to noise. It was demonstrated that an alternate mechanism, phantom bursting, was very sensitive to noise, and therefore could not account for the slow bursting in single cells. We re-examine these conclusions, motivated by recent experimental and mathematical modeling evidence that slow bursting in intact islets is, at least in many cases, driven by the phantom bursting mechanism and not endogenous glycolytic oscillations. We employ two phantom bursting models, one minimal and the other more biophysical, to determine the sensitivity of medium and slow bursting to electrical current noise. In the minimal model, both forms of bursting are highly sensitive to noise. In the biophysical model, while medium bursting is sensitive to noise, slow bursting is much less sensitive. This suggests that the slow bursting seen in isolated β-cellsmay be due to a phantom bursting mechanism, and by extension, slow bursting in intact islets may also be driven by this mechanism.