WHY PANCREATIC-ISLETS BURST BUT SINGLE BETA-CELLS DO NOT - THE HETEROGENEITY HYPOTHESIS

Previous mathematical modeling of beta cell electrical activity has in volved single cells or, recently, clusters of identical cells. Here we model clusters of heterogeneous cells that differ in size, channel de nsity, and other parameters. We use gap-junctional electrical coupling , with conductances determined by an experimental histogram. We find t hat, for reasonable parameter distributions, only a small proportion o f isolated beta cells will burst when uncoupled, at any given value of a glucose-sensing parameter. However, a coupled, heterogeneous cluste r of such cells, if sufficiently large (approximately 125 cells), will burst synchronously. Small clusters of such cells will burst only wit h low probability. In large clusters, the dynamics of intracellular ca lcium compare well with experiments. Also, these clusters possess a do se-response curve of increasing average electrical activity with respe ct to a glucose-sensing parameter that is sharp when the cluster is co upled, but shallow when the cluster is decoupled into individual cells . This is in agreement with comparative experiments on cells in suspen sion and islets.