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

Min Zhang ^*, Paula Goforth ^*, Richard Bertram , Arthur Sherman  and Leslie Satin ^*

^* Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia; Department of Mathematics and Kasha Laboratory of Biophysics, Florida State University, Tallahassee, Florida; and Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Correspondence: Address reprint requests to Dr. L. S. Satin, Dept. of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, PO Box 980524, Richmond, VA 23298 USA. Tel.: 804-828-7823; E-mail: lsatin{at}hsc.vcu.edu.

[Ca²⁺]_i and electrical activity were compared in isolated ß-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 ß-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 ß-cell electrical activity. Whereas islets exhibited bursts of spikes on medium/slow plateaus, isolated ß-cells were depolarized and exhibited spiking, fast-bursting, or spikeless plateaus. These electrical patterns in turn produced distinct [Ca²⁺]_i patterns. Thus, although isolated ß-cells display several key features of islets, their oscillations were faster and more irregular. ß-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 ß-cell [Ca²⁺]_i changes followed membrane potential, suggesting that electrical activity is mainly responsible for the [Ca²⁺] dynamics of ß-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 ß-cells, suggesting that these behaviors reflect natural cell heterogeneity. These results support our recent model and point to the important role of ß-cell electrical events in controlling [Ca²⁺]_i over diverse time scales in islets.

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