The Ca2+ dynamics of isolated mouse β-cells and islets:: Implications for mathematical models

[Ca2+](i) and electrical activity were compared in isolated beta-cells and islets using standard techniques. In islets, raising glucose caused a decrease in [Ca2+](i) followed by a plateau and then fast (2-3 min(-1)), slow (0.2-0.8 min(-1)), or a mixture of fast and slow [Ca2+](i) oscillations. In beta-cells, glucose transiently decreased and then increased [Ca2+](i), but no islet-like oscillations occurred. Simultaneous recordings of [Ca2+](i) and electrical activity suggested that differences in [Ca2+](i) signaling are due to differences in islet versus beta-cell electrical activity. Whereas islets exhibited bursts of spikes on medium/slow plateaus, isolated P-cells were depolarized and exhibited spiking, fast-bursting, or spikeless plateaus. These electrical patterns in turn produced distinct [Ca2+](i) patterns. Thus, although isolated beta-cel Is display several key features of islets, their oscillations were faster and more irregular. beta-cells could display islet-like [Ca2+](i) oscillations if their electrical activity was converted to a slower islet-like pattern using dynamic clamp. Islet and beta-cell [Ca2+](i) changes followed membrane potential, suggesting that electrical activity is mainly responsible for the [Ca2+](i) dynamics of beta-cells and islets. A recent model consisting of two slow feedback processes and passive endoplasmic reticulum. Ca2+ release was able to account for islet [Ca2+](i) responses to glucose, islet oscillations, and conversion of single cell to islet-like [Ca2+](i) oscillations. With minimal parameter variation, the model could also account for the diverse behaviors of isolated beta-cells, suggesting that these behaviors reflect natural cell heterogeneity. These results support our recent model and point to the important role of beta-cell electrical events in controlling [Ca2+](i) over diverse time scales in islets.