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Expression and Regulation of Types I and II Inositol 1,4,5‐Trisphosphate Receptors in Rat Cerebellar Granule Cell Preparations
Author(s) -
Oberdorf Jon,
Vallano Mary Lou,
Wojcikiewicz Richard J. H.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69051897.x
Subject(s) - inositol , granule cell , receptor , biology , microbiology and biotechnology , metabotropic receptor , muscarinic acetylcholine receptor , inositol phosphate , granule (geology) , carbachol , inositol trisphosphate , cell type , cerebellum , biochemistry , agonist , cell , endocrinology , central nervous system , paleontology , dentate gyrus
Previous studies have shown that as rat cerebellar granule cell cultures differentiate in the presence of 25 m M KCl, they “up‐regulate” their ability to form inositol phosphates and release Ca 2+ from internal stores in response to the activation of phosphoinositidase C‐linked muscarinic and metabotropic receptors. Here we show that they simultaneously up‐regulate their ability to respond to inositol 1,4,5‐trisphosphate (InsP 3 ) by increasing InsP 3 receptor (InsP 3 R) expression. In contrast, if granule cells are maintained at the more physiological KCl concentration of 5 m M , most cells undergo apoptosis, although a significant number survive. The surviving cells, however, express few InsP 3 Rs, suggesting that an influx of Ca 2+ through voltage‐dependent channels is required for InsP 3 R up‐regulation. In addition, we have determined that these cultures express two genetically distinct InsP 3 R types, but that only one, the type I receptor, is expressed in granule cells. Type II receptors are also present but are found exclusively in astrocytes, which are a minor contaminant of granule cell cultures. This segregation of InsP 3 R types explains a previous observation, showing that the muscarinic agonist carbachol causes the reduction or “down‐regulation” of type I but not type II InsP 3 Rs.