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

Abstract

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