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

• Published in: Endocrinology (Philadelphia) Vol. 146; no. 11; pp. 4766 - 4775
• Main Authors: Leung, Yuk M, Ahmed, Ishtiaq, Sheu, Laura, Tsushima, Robert G, Diamant, Nicholas E, Hara, Manami, Gaisano, Herbert Y
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.11.2005
• Subjects: Adenosine Triphosphate - metabolism; Adenosine Triphosphate - pharmacology; Animals; Biological and medical sciences; Calcium Channels - physiology; Electrophysiology; Exocytosis; Fundamental and applied biological sciences. Psychology; Green Fluorescent Proteins - genetics; In Vitro Techniques; Insulin - genetics; Islets of Langerhans - cytology; Islets of Langerhans - metabolism; Islets of Langerhans - physiology; Mice; Mice, Transgenic - physiology; Microscopy, Confocal; Microscopy, Fluorescence; Potassium Channels - drug effects; Potassium Channels - physiology; Potassium Channels, Voltage-Gated - physiology; Promoter Regions, Genetic; Sodium Channels - physiology; Vertebrates: endocrinology; Characterization; Pancreatic hormone; Vertebrata; Mammalia; Mouse; Animal; Rodentia; Langerhans islet; Green fluorescent protein; Electrophysiology; Insulin; Endocrine pancreas
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2005-0803

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.