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This version published online on August 18, 2005
Endocrinology, doi:10.1210/en.2005-0803
A more recent version of this article appeared on November 1, 2005
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Submitted on June 29, 2005
Accepted on August 11, 2005

Electrophysiological Characterization of Pancreatic Islet Cells in the MIP-GFP Mouse

Yuk M. Leung*, Ishtiaq Ahmed, Laura Sheu, Robert G. Tsushima, Nicholas E. Diamant, Manami Hara, and Herbert Y. Gaisano

Departments of Medicine and Physiology, University of Toronto, Toronto, Canada, M5S 1A8; Department of Medicine, University of Chicago, Chicago, IL 60637, USA

* To whom correspondence should be addressed. E-mail: yukman.leung{at}utoronto.ca.

We recently reported a transgenic (Mouse Insulin Promoter-Green Fluorescent Protein; MIP-GFP) mouse in which GFP expression is targeted to the pancreatic islet {beta}-cells to enable convenient identification of {beta}-cells as green cells. The GFP-expressing {beta}-cells of the MIP-GFP mouse were functionally indistinguishable from {beta}-cells of normal mice. Here we characterized the ionic channel properties and exocytosis of MIP-GFP mouse islet {beta}- and {alpha}-cells. {beta}-cells displayed delayed rectifying K+ and high-voltage-activated (HVA) Ca2+ channels, and exhibited Na+ currents only at hyperpolarized holding potential (VH). {alpha}-cells were non-green and had both A-type and delayed rectifier K+ channels, both low-voltage-activated (LVA) and HVA Ca2+ channels, and displayed Na+ currents readily at -70 mV VH. {alpha}-cells had KATP channel density as high as that in {beta}-cells, and surprisingly, {alpha}-cell KATP channels were more sensitive to ATP inhibition (IC50 = 0.16 ± 0.03 mM) than {beta}-cell KATP channels (IC50 = 0.86 ± 0.10 mM). While {alpha}-cells were rather uniform in size (2-4.5 pF), {beta}-cells varied vastly in size (2-12 pF). Of note, small {beta}-cells (<4.5 pF) showed little exocytosis, whereas medium {beta}-cells (5-8 pF) exhibited vigorous exocytosis, but large {beta}-cells (>8 pF) had weaker exocytosis. We found no correlation between {beta}-cell size and their Ca2+ channel density, suggesting that Ca2+ influx may not be the cause of the heterogeneity in exocytotic responses. The MIP-GFP mouse therefore offers potential to further explore the functional heterogeneity in {beta}-cells of different sizes. The MIP-GFP mouse islet is therefore a reliable model to efficiently examine {alpha}-cell and {beta}-cell physiology, and should greatly facilitate examination of their pathophysiology when the MIP-GFP mice are crossed with diabetic models.


Key words: islet {alpha}-cells • islet {beta}-cells • ion channels • exocytosis • electrophysiology • capacitance measurements




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