The Calcium Dynamics of Isolated Mouse Beta-Cells and Islets: Implications for Mathematical Models
M. Zhang, P. Goforth, R. Bertram, A. Sherman, L. Satin
Calcium and electrical activity were compared in isolated Beta-cells and islets using standard techniques. In islets, raising glucose caused a decrease in calcium 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 calcium oscillations. In Beta-cells, glucose transiently decreased and then increased calcium, but no islet-like oscillations occurred. Simultaneous recordings of calcium and electrical activity suggested that differences in calcium signaling are due to differences in islet versus Beta-cell electrical activity. Whereas islets exhibited bursts of spikes on medium/slow plateaus, isolated Beta-cells were depolarized and exhibited spiking, fast-bursting, or spikeless plateaus. These electrical patterns in turn produced distinct calcium patterns. Thus, although isolated Beta-cells display several key features of islets, their oscillations were faster and more irregular. Beta-cells could display islet-like calcium oscillations if their electrical activity was converted to a slower islet-like pattern using dynamic clamp. Islet and Beta-cell calcium changes followed membrane potential, suggesting that electrical activity is mainly responsible for the calcium dynamics of Beta-cells and islets. A recent model consisting of two slow feedback processes and passive endoplasmic reticulum calcium release was able to account for islet calcium responses to glucose, islet oscillations, and conversion of single cell to islet-like calcium 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 calcium over diverse time scales in islets.