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Electrophysiological Characterization of Pancreatic Islet Cells in the Mouse Insulin Promoter-Green Fluorescent Protein Mouse

Departments of Medicine and Physiology (Y.M.L., I.A., L.S., R.G.T., N.E.D., H.Y.G.), University of Toronto, Toronto, Canada M5S 1A8; and Department of Medicine (M.H.), University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: Dr. Yuk M. Leung, Room 7308, or Dr. Herbert Y. Gaisano, Room 7226, Medical Sciences Building, 1 King’s College Circle, University of Toronto, Toronto, Ontario M5S 1A8, Canada. E-mail: yukman.leung{at}utoronto.ca or herbert.gaisano{at}utoronto.ca.

We recently reported a transgenic [mouse insulin promoter (MIP)-green fluorescent protein (GFP)] mouse in which GFP expression is targeted to the pancreatic islet ß-cells to enable convenient identification of ß-cells as green cells. The GFP-expressing ß-cells of the MIP-GFP mouse were functionally indistinguishable from ß-cells of normal mice. Here we characterized the ionic channel properties and exocytosis of MIP-GFP mouse islet ß- and -cells. ß-Cells displayed delayed rectifying K⁺ and high-voltage-activated Ca²⁺ channels and exhibited Na⁺ currents only at hyperpolarized holding potential. -Cells were nongreen and had both A-type and delayed rectifier K⁺ channels, both low-voltage-activated and high-voltage-activated Ca²⁺ channels, and displayed Na⁺ currents readily at –70 mV holding potential. -Cells had ATP-sensitive K⁺ channel (K_ATP) channel density as high as that in ß-cells, and, surprisingly, -cell K_ATP channels were more sensitive to ATP inhibition (IC₅₀ = 0.16 ± 0.03 mM) than ß-cell K_ATP channels (IC₅₀ = 0.86 ± 0.10 mM). Whereas -cells were rather uniform in size [2–4.5 picofarad (pF)], ß-cells varied vastly in size (2–12 pF). Of note, small ß-cells (<4.5 pF) showed little exocytosis, whereas medium ß-cells (5–8 pF) exhibited vigorous exocytosis, but large ß-cells (>8 pF) had weaker exocytosis. We found no correlation between ß-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 ß-cells of different sizes. The MIP-GFP mouse islet is therefore a reliable model to efficiently examine -cell and ß-cell physiology and should greatly facilitate examination of their pathophysiology when the MIP-GFP mice are crossed with diabetic models.

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