title: Comparison of and chromogranin effect on inositol 1,4,5-trisphosphate sensitivity of cytoplasmic and nucleoplasmic inositol 1,4,5-trisphosphate receptor/Ca2+ channels.
abstract: The nucleus also contains the inositol 1,4,5-trisphosphate receptor (IP3R)/Ca2+ channels in the nucleoplasm proper independent of the nuclear envelope or the cytoplasm. The nuclear IP3R/Ca2+ channels were shown to be present in small IP3-dependent nucleoplasmic Ca2+ store vesicles, yet no information is available regarding the IP3 sensitivity of nuclear IP3R/Ca2+ channels. Here, we show that nuclear IP3R/Ca2+ channels are 3-4-fold more sensitive to IP3 than cytoplasmic ones in both neuroendocrine PC12 cells and nonneuroendocrine NIH3T3 cells. Given the presence of phosphoinositides and phospholipase C and the importance of IP3-mediated Ca2+ signaling in the nucleus, the high IP3 sensitivity of nuclear IP3R/Ca2+ channels seemed to reflect the physiological needs of the nucleus to finely control the IP3-dependent Ca2+ concentrations. It was further shown that the IP3R/Ca2+ channels of secretory cells are 7-8-fold more sensitive to IP3 than those of nonsecretory cells. This difference appeared to result from the presence of secretory cell marker protein chromogranins (thus secretory granules) in secretory cells; expression of chromogranins in NIH3T3 cells increased the IP3 sensitivity of both nuclear and cytoplasmic IP3R/Ca2+ channels by approximately 4-6-fold. In contrast, suppression of chromogranin A expression in PC12 cells changed the EC50 of IP3 sensitivity for cytoplasmic IP3R/Ca2+ channels from 17 to 47 nM, whereas suppression of chromogranin B expression changed the EC50 of cytoplasmic IP3R/Ca2+ channels from 17 to 102 nM and the nuclear ones from 4.3 to 35 nM. Given that secretion is the major function of secretory cells and is under a tight control of intracellular Ca2+ concentrations, the high IP3 sensitivity appears to reflect the physiological roles of secretory cells.
authors.affiliation: Department of Biochemistry, Inha University College of Medicine, Jung Gu, Incheon 400-712, Korea.
authors.forename: Yang Hoon
authors.initials: YH
authors.lastname: Huh
authors.forename: Ki Deok
authors.initials: KD
authors.lastname: Kim
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Yoo
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002467:Cell Nucleus / Q000187:drug effects; D053379:Chromogranin A / Q000494:pharmacology*; D053378:Chromogranin B / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000187:drug effects*; D051379:Mice; D041681:NIH 3T3 Cells; D016716:PC12 Cells; D051381:Rats
chemical_list: D053379:Chromogranin A; D053378:Chromogranin B; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium