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

Objectives The and 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 and cells of rat pancreas. Results All 3 IP3R isoforms were present in SG membranes of both cells, and the IP3R concentrations in SGs were approximate to 2-fold higher than those in the endoplasmic reticulum. Moreover, large halos shown in the electron microscope images of insulin-containing SGs of 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 cells was further confirmed by the location of another integral membrane protein synaptotagmin V and of membrane phospholipid PI(4,5)P-2.