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Submitted on June 29, 2005
Accepted on August 11, 2005
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
-cells to enable convenient identification of
-cells as green cells. The GFP-expressing
-cells of the MIP-GFP mouse were functionally indistinguishable from
-cells of normal mice. Here we characterized the ionic channel properties and exocytosis of MIP-GFP mouse islet
- and
-cells.
-cells displayed delayed rectifying K+ and high-voltage-activated (HVA) Ca2+ channels, and exhibited Na+ currents only at hyperpolarized holding potential (VH).
-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.
-cells had KATP channel density as high as that in
-cells, and surprisingly,
-cell KATP channels were more sensitive to ATP inhibition (IC50 = 0.16 ± 0.03 mM) than
-cell KATP channels (IC50 = 0.86 ± 0.10 mM). While
-cells were rather uniform in size (2-4.5 pF),
-cells varied vastly in size (2-12 pF). Of note, small
-cells (<4.5 pF) showed little exocytosis, whereas medium
-cells (5-8 pF) exhibited vigorous exocytosis, but large
-cells (>8 pF) had weaker exocytosis. We found no correlation between
-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
-cells of different sizes. The MIP-GFP mouse islet is therefore a reliable model to efficiently examine
-cell and
-cell physiology, and should greatly facilitate examination of their pathophysiology when the MIP-GFP mice are crossed with diabetic models.
-cells
islet
-cells
ion channels
exocytosis
electrophysiology
capacitance measurements
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