Distribution Profile of Inositol 1,4,5-Trisphosphate Receptor/Ca2+ Channels in α and β Cells of Pancreas: Dominant Localization in Secretory Granules and Common Error in Identification of Secretory Granule Membranes

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Abstract

Objectives

The α and β cells of pancreatic islet release important hormones in response to intracellular Ca2+ increases that result from Ca2+ releases through the inositol 1,4,5-trisphoshate receptor (IP3R)/Ca2+ channels. Yet no systematic studies on distribution of IP3R/Ca2+ channels have been done, prompting us to investigate the distribution of all 3 IP3R isoforms.

Methods

Immunogold electron microscopy was performed to determine the presence and the relative concentrations of all 3 IP3R isoforms in 2 major organelles secretory granules (SGs) and the endoplasmic reticulum of α and β cells of rat pancreas.

Results

All 3 IP3R isoforms were present in SG membranes of both cells, and the IP3R concentrations in SGs were ∼2-fold higher than those in the endoplasmic reticulum. Moreover, large halos shown in the electron microscope images of insulin-containing SGs of β cells were gap spaces that resulted from separation of granule membranes from the surrounding cytoplasm.

Conclusions

These results strongly suggest the important roles of SGs in IP3-induced, Ca2+-dependent regulatory secretory pathway in pancreas. Moreover, the accurate location of SG membranes of β cells was further confirmed by the location of another integral membrane protein synaptotagmin V and of membrane phospholipid PI(4,5)P2.

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