The Ca2+ Dynamics of Isolated Mouse β-Cells and Islets: Implications for Mathematical Models

Ca]i and electrical activity were compared in isolated b-cells and islets using standard techniques. In islets, raising glucose caused a decrease in [Ca]i followed by a plateau and then fast (2 3 min ), slow (0.2–0.8 min ), or a mixture of fast and slow [Ca]i oscillations. In b-cells, glucose transiently decreased and then increased [Ca ]i, but no islet-like oscillations occurred. Simultaneous recordings of [Ca]i and electrical activity suggested that differences in [Ca ]i signaling are due to differences in islet versus b-cell electrical activity. Whereas islets exhibited bursts of spikes on medium/slow plateaus, isolated b-cells were depolarized and exhibited spiking, fast-bursting, or spikeless plateaus. These electrical patterns in turn produced distinct [Ca]i patterns. Thus, although isolated b-cells display several key features of islets, their oscillations were faster and more irregular. b-cells could display islet-like [Ca]i oscillations if their electrical activity was converted to a slower islet-like pattern using dynamic clamp. Islet and b-cell [Ca]i changes followed membrane potential, suggesting that electrical activity is mainly responsible for the [Ca] dynamics of b-cells and islets. A recent model consisting of two slow feedback processes and passive endoplasmic reticulum Ca release was able to account for islet [Ca]i responses to glucose, islet oscillations, and conversion of single cell to islet-like [Ca]i oscillations. With minimal parameter variation, the model could also account for the diverse behaviors of isolated b-cells, suggesting that these behaviors reflect natural cell heterogeneity. These results support our recent model and point to the important role of b-cell electrical events in controlling [Ca]i over diverse time scales in islets.