Document Type

Article

Original Publication Date

2003

Journal/Book/Conference Title

The Biophysical Journal

Volume

84

Issue

5

First Page

2852

Last Page

2870

DOI of Original Publication

10.1016/S0006-3495(03)70014-9

Comments

Originally published at http://dx.doi.org/10.1016/S0006-3495(03)70014-9

Under an Elsevier user license

Date of Submission

February 2015

Abstract

ABSTRACT

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

Rights

From The Biophysical Journal, Zhang, M., Goforth, P., Bertram, R., et al., The Ca2+ Dynamics of Isolated Mouse β-Cells and Islets: Implications for Mathematical Models, Vol. 84, Page 2852. Copyright © 2003 The Biophysical Society. Published by Elsevier Inc. Reprinted with permission.

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VCU Pharmacology and Toxicology Publications

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