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Keiji Hirata, Michael H. Nathanson, Angela D. Burgstahler, Keisuke Okazaki, Elisabetta Mattei, Marvin L. Sears; Relationship between Inositol 1,4,5-Trisphosphate Receptor Isoforms and Subcellular Ca2+ Signaling Patterns in Nonpigmented Ciliary Epithelia. Invest. Ophthalmol. Vis. Sci. 1999;40(9):2046-2053.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. Subcellular Ca2+ signaling patterns, such as
Ca2+ waves, gradients, and oscillations, are an important
aspect of cell regulation, but the molecular basis for these signaling
patterns is not understood. Because Ca2+ release patterns
differ among isoforms of the inositol 1,4,5-trisphosphate (InsP3)
receptor, the relationship between the distribution of these
isoforms and subcellular Ca2+ signaling patterns in
nonpigmented epithelial (NPE) cells was investigated.
methods. The distributions of the types I, II, and III InsP3 receptors were
determined in NPE cells by immunofluorescence, and subcellular
Ca2+ signaling patterns in these cells were examined by
confocal line scanning microscopy.
results. The type I InsP3 receptor was concentrated at the basal pole of NPE
cells, whereas the type III receptor was localized to the apical pole.
The type II InsP3 receptor was not expressed in detectable amounts.
Acetylcholine induced increases in Ca2+ that were mediated
by InsP3, and these Ca2+ increases began as
Ca2+ waves that were initiated at the apical pole, in the
region of the type III InsP3 receptor. Acetylcholine occasionally
induced sustained or repetitive Ca2+ increases that were
prominent at the basal pole, in the region of the type I InsP3
receptor, but only subtle or absent apically.
conclusions. Because the type I InsP3 receptor is thought to be responsible for
repetitive Ca2+ release events, and the type III InsP3
receptor instead is suited to initiate Ca2+ signals, the
subcellular distribution of these two isoforms corresponds to the
Ca2+ signaling patterns observed in this cell type.
Differential subcellular expression of InsP3 receptor isoforms may be
an important molecular mechanism by which NPE cells organize their
Ca2+ signals in space and time.
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