Expression and regulation of types I and II inositol 1,4,5-trisphosphate receptors in rat cerebellar granule cell preparations.
Previous studies have shown that as rat cerebellar granule cell cultures differentiate in the presence of 25 mM KCl, they "up-regulate" their ability to form inositol phosphates and release Ca2+ 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 (InsP3) by increasing InsP3 receptor (InsP3R) expression. In contrast, if granule cells are maintained at the more physiological KCl concentration of 5 mM, most cells undergo apoptosis, although a significant number survive. The surviving cells, however, express few InsP3Rs, suggesting that an influx of Ca2+ through voltage-dependent channels is required for InsP3R up-regulation. In addition, we have determined that these cultures express two genetically distinct InsP3R 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 InsP3R types explains a previous observation, showing that the muscarinic agonist carbachol causes the reduction or "down-regulation" of type I but not type II InsP3Rs.
Oberdorf
J
J
Department of Pharmacology, SUNY Health Science Center, Syracuse 13210-2339, U.S.A.
Vallano
M L
ML
Wojcikiewicz
R J
RJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015220:Calcium Channels / Q000096:biosynthesis*; D002217:Carbachol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D016900:Neurofilament Proteins / Q000096:biosynthesis; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D016900:Neurofilament Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011189:Potassium Chloride; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol