Emergence of organized bursting in clusters of pancreatic beta-cells by channel sharing

Abstract

Pancreatic beta-cells in an intact Islet of Langerhans exhibit bursting electrical behavior. The Chay-Keizer model describes this using a calcium-activated potassium (K-Ca) channel, but cannot account for the irregular spiking of isolated beta-cells. Atwater I., L. Rosario, and E. Rojas, Cell Calcium. 4:451-461, proposed that the K-Ca channels, which are rarely open, are shared by several cells. This suggests that the chaotic behavior of isolated cells is stochastic. We have revised the Chay-Keizer model to incorporate voltage clamp data of Rorsman and Trube and extended it to include stochastic K-Ca channels. This model can describe the behavior of single cells, as well as that of clusters of cells tightly coupled by gap junctions. As the size of the clusters is increased, the electrical activity shows a transition from chaotic spiking to regular bursting. Although the model of coupling is over-simplified, the simulations lend support to the hypothesis that bursting is the result of channel sharing.

Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells

“…These bursts of action potentials are likely to underlie the intracellular Ca 2+ concentration [Ca 2+ ] i oscillations reported in delta cells [11,12,21,22], although the frequency of the [Ca 2+ ] i oscillations was slightly lower (<1/min) than that of the electrical bursts observed here (2-5/min). It has been proposed, based on both experimental and theoretical considerations, that oscillatory electrical activity in mouse beta cells depends on cell coupling [23,24]. However, the finding that high-frequency bursts of action potentials can be recorded from individual human delta cells suggests that cell coupling is not required for such electrical activity to occur.…”

Complex bursting in pancreatic islets: a potential glycolytic mechanism

“…Some more complete models for glycolytic oscillations include those by Smolen (Smolen, 1995), Tornheim (1979), and Westermark and Lansner (2003). More recent models of bursting in b-cells include those by Chay (1996), Keizer and Smolen (1989), and Sherman et al (1988). In one recent b-cell model, the Phantom Bursting Model (PBM), bursting is driven by the interaction of more than one slow variable Goforth et al, 2002).…”

“…Several models have been developed for bursting in pancreatic b-cells Chay, 1996;Chay and Keizer, 1983;Goforth et al, 2002;Keizer and Smolen, 1991;Sherman et al, 1988). These models differ primarily in the slow process responsible for driving the bursting.…”

From Spikers to Bursters Via Coupling: Help From Heterogeneity

“…According to the first, in isolated cells, noise from stochastic channel fluctuations shortens or eliminates the bursts by causing premature transitions between silent and active phases. In large populations, on the other hand, the fluctuations are damped, allowing the underlying burst dynamics to become manifest (Sherman et al, 1988). The second hypothesis emphasizes heterogeneity: single cell properties are very variable (Kinard et al, 1999), and individual cells may fall outside the narrow parameter regime required for bursting.…”