Gap Junction Coupling and Calcium Waves in the Pancreatic Islet

Authors

Richard K.P. Benninger, Vanderbilt UniversityFollow
Min Zhang, Virginia Commonwealth University
W. Steven Head, Vanderbilt University
Leslie S. Satin, Virginia Commonwealth University, University of Michigan
David W. Piston, Vanderbilt University

Document Type

Article

Original Publication Date

2008

Journal/Book/Conference Title

The Biophysical Journal

Volume

95

Issue

11

First Page

5048

Last Page

5061

DOI of Original Publication

10.1529/biophysj.108.140863

Comments

Originally published at http://dx.doi.org/10.1529/biophysj.108.140863

Under an Elsevier user license

Date of Submission

February 2015

Abstract

Abstract

The pancreatic islet is a highly coupled, multicellular system that exhibits complex spatiotemporal electrical activity in response to elevated glucose levels. The emergent properties of islets, which differ from those arising in isolated islet cells, are believed to arise in part by gap junctional coupling, but the mechanisms through which this coupling occurs are poorly understood. To uncover these mechanisms, we have used both high-speed imaging and theoretical modeling of the electrical activity in pancreatic islets under a reduction in the gap junction mediated electrical coupling. Utilizing islets from a gap junction protein connexin 36 knockout mouse model together with chemical inhibitors, we can modulate the electrical coupling in the islet in a precise manner and quantify this modulation by electrophysiology measurements. We find that after a reduction in electrical coupling, calcium waves are slowed as well as disrupted, and the number of cells showing synchronous calcium oscillations is reduced. This behavior can be reproduced by computational modeling of a heterogeneous population of β-cells with heterogeneous levels of electrical coupling. The resulting quantitative agreement between the data and analytical models of islet connectivity, using only a single free parameter, reveals the mechanistic underpinnings of the multicellular behavior of the islet.

Rights

From The Biophysical Journal, Benninger, R.K.P., Zhang, M., Head, W.S., Gap Junction Coupling and Calcium Waves in the Pancreatic Islet, Vol. 95, Page 5048. Copyright © 2008 The Biophysical Society. Published by Elsevier Inc. Reprinted with permission.

Is Part Of

VCU Pharmacology and Toxicology Publications