Regulation of Ca2+signaling in rat bile duct epithelia by inositol 1,4,5-trisphosphate receptor isoforms
Open Access
- 1 August 2002
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 36 (2), 284-296
- https://doi.org/10.1053/jhep.2002.34432
Abstract
Cytosolic Ca2+ (Cai2+) regulates secretion of bicarbonate and other ions in the cholangiocyte. In other cell types, this second messenger acts through Ca2+ waves, Ca2+ oscillations, and other subcellular Ca2+ signaling patterns, but little is known about the subcellular organization of Ca2+ signaling in cholangiocytes. Therefore, we examined Ca2+ signaling and the subcellular distribution of Ca2+ release channels in cholangiocytes and in a model cholangiocyte cell line. The expression and subcellular distribution of inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) isoforms and the ryanodine receptor (RyR) were determined in cholangiocytes from normal rat liver and in the normal rat cholangiocyte (NRC) polarized bile duct cell line. Subcellular Ca2+ signaling in cholangiocytes was examined by confocal microscopy. All 3 InsP3R isoforms were expressed in cholangiocytes, whereas RyR was not expressed. The type III InsP3R was the most heavily expressed isoform at the protein level and was concentrated apically, whereas the type I and type II isoforms were expressed more uniformly. The type III InsP3R was expressed even more heavily in NRC cells but was concentrated apically in these cells as well. Adenosine triphosphate (ATP), which increases Ca2+ via InsP3 in cholangiocytes, induced Ca2+ oscillations in both cholangiocytes and NRC cells. Acetylcholine (ACh) induced apical-to-basal Ca2+ waves. In conclusion, Ca2+ signaling in cholangiocytes occurs as polarized Ca2+ waves that begin in the region of the type III InsP3R. Differential subcellular localization of InsP3R isoforms may be an important molecular mechanism for the formation of Ca2+ waves and oscillations in cholangiocytes. Because Cai2+ is in part responsible for regulating ductular secretion, these findings also may have implications for the molecular basis of cholestatic disorders.Keywords
Funding Information
- National Institutes of Health (DK45710, DK57751, TW01451, DK34989)
- Cystic Fibrosis Foundation, and the American Heart Association (to M.H.N.); Swiss National Foundation to J.-F.D. (3100-063696.00)
- Swiss National Foundation to M.V.S. (3234055037.98)
- Association pour la Recherche sur le Cancer (6551)
- INSERM to D.C. (contrat PRISME 98-09)
This publication has 53 references indexed in Scilit:
- Expression of inositol 1,4,5-trisphosphate receptor isoforms in rat cirrhosisHepatology, 1999
- Polarized Expression of Ca2+ Channels in Pancreatic and Salivary Gland CellsJournal of Biological Chemistry, 1997
- Type I, II, and III Inositol 1,4,5-Trisphosphate Receptors Are Unequally Susceptible to Down-regulation and Are Expressed in Markedly Different Proportions in Different Cell TypesJournal of Biological Chemistry, 1995
- The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues.The Journal of cell biology, 1995
- Regulation of membrane chloride currents in rat bile duct epithelial cells.JCI Insight, 1993
- Patterns of elevated free calcium and calmodulin activation in living cellsNature, 1992
- Bell-shaped calcium-response curves of lns(l,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellumNature, 1991
- Simultaneous measurements of cytosolic calcium and secretion in single bovine adrenal chromaffin cells by fluorescent imaging of fura-2 in cocultured cells.The Journal of cell biology, 1989
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970