title: InsP3 signaling induces pulse-modulated Ca2+ signals in the nucleus of airway epithelial ciliated cells.
abstract: The phenomenology of nuclear Ca(2+) dynamics has experienced important progress revealing the broad range of cellular processes that it regulates. Although several agonists can mobilize Ca(2+) from storage in the nuclear envelope (NE) to the intranuclear compartment (INC), the mechanisms of Ca(2+) signaling in the nucleus still remain uncertain. Here we report that the NE/INC complex can function as an inositol-1,4,5-trisphosphate (InsP(3))-controlled Ca(2+) oscillator. Thin optical sectioning combined with fluorescent labeling of Ca(2+) probes show in cultured airway epithelial ciliated cells that ATP can trigger periodic oscillations of Ca(2+) in the NE ([Ca(2+)](NE)) and corresponding pulses of Ca(2+) release to the INC. Identical results were obtained in InsP(3)-stimulated isolated nuclei of these cells. Our data show that [Ca(2+)](NE) oscillations and Ca(2+) release to the INC result from the interplay between the Ca(2+)/K(+) ion-exchange properties of the intralumenal polyanionic matrix of the NE and two Ca(2+)-sensitive ion channels-an InsP(3)-receptor-Ca(2+) channel and an apamin-sensitive K(+) channel. A similar Ca(2+) signaling system operating under the same functional protocol and molecular hardware controls Ca(2+) oscillations and release in/to the endoplasmic reticulum/cytosol and in/to the granule/cytosol complexes in airway and mast cells. These observations suggest that these intracellular organelles share a remarkably conserved mechanism of InsP(3)-controlled frequency-encoded Ca(2+) signaling.
authors.affiliation: Department of Bioengineering and Friday Harbor Laboratories, University of Washington, Seattle, 98195, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Quesada
authors.forename: Pedro
authors.initials: P
authors.lastname: Verdugo
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D015544:Inositol 1,4,5-Trisphosphate