Electrophysiological characterization of pancreatic islet cells in the mouse insulin promoter-green fluorescent protein mouse

We recently reported a transgenic [ mouse insulin promoter ( MIP)- green fluorescent protein ( 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 MIPGFP mouse islet beta- and alpha- cells. beta- Cells displayed delayed rectifying K+ and high- voltage- activated Ca2+ channels and exhibited Na+ currents only at hyperpolarized holding potential. alpha- 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 -70mV holding potential. alpha- Cells had ATP- sensitive K+ channel ( KATP) channel density as high as that in beta- cells, and, surprisingly, alpha- cell K-ATP channels were more sensitive ATP inhibition ( IC50 = 0.16 +/- 0.03 mM) than beta- cell K-ATP channels ( IC50 = 0.86 +/- 0.10 mM). Whereas alpha- cells were rather uniform in size [ 2 - 4.5 picofarad ( 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 ound 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.