Gap junction coupling and calcium waves in the pancreatic islet |
| |
Authors: | Benninger Richard K P Zhang Min Head W Steven Satin Leslie S Piston David W |
| |
Institution: | * Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee † Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia ‡ Department of Pharmacology and Brehm Diabetes Center, University of Michigan, Ann Arbor, Michigan |
| |
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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|