This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.105.061390v1 88/6/3946    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Quesada, I. Articles by Verdugo, P. Search for Related Content PubMed PubMed Citation Articles by Quesada, I. Articles by Verdugo, P.

InsP₃ Signaling Induces Pulse-Modulated Ca²⁺ Signals in the Nucleus of Airway Epithelial Ciliated Cells

Department of Bioengineering and Friday Harbor Laboratories, University of Washington, Seattle, Washington 98195

Correspondence: Address reprint requests to Pedro Verdugo, Friday Harbor Laboratories, University of Washington, 620 University Road, Friday Harbor, WA 98250. Tel.: 206-543-5994, 206-685-2003; Fax: 206-543-1273; E-mail: verdugo{at}u.washington.edu.

The phenomenology of nuclear Ca²⁺ dynamics has experienced important progress revealing the broad range of cellular processes that it regulates. Although several agonists can mobilize Ca²⁺ from storage in the nuclear envelope (NE) to the intranuclear compartment (INC), the mechanisms of Ca²⁺ signaling in the nucleus still remain uncertain. Here we report that the NE/INC complex can function as an inositol-1,4,5-trisphosphate (InsP₃)-controlled Ca²⁺ oscillator. Thin optical sectioning combined with fluorescent labeling of Ca²⁺ probes show in cultured airway epithelial ciliated cells that ATP can trigger periodic oscillations of Ca²⁺ in the NE ([Ca²⁺]_NE) and corresponding pulses of Ca²⁺ release to the INC. Identical results were obtained in InsP₃-stimulated isolated nuclei of these cells. Our data show that [Ca²⁺]_NE oscillations and Ca²⁺ release to the INC result from the interplay between the Ca²⁺/K⁺ ion-exchange properties of the intralumenal polyanionic matrix of the NE and two Ca²⁺-sensitive ion channels—an InsP₃-receptor-Ca²⁺ channel and an apamin-sensitive K⁺ channel. A similar Ca²⁺ signaling system operating under the same functional protocol and molecular hardware controls Ca²⁺ 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 InsP₃-controlled frequency-encoded Ca²⁺ signaling.

This article has been cited by other articles:

				V. Kumar, Y.-J. I. Jong, and K. L. O'Malley Activated Nuclear Metabotropic Glutamate Receptor mGlu5 Couples to Nuclear Gq/11 Proteins to Generate Inositol 1,4,5-Trisphosphate-mediated Nuclear Ca2+ Release J. Biol. Chem., May 16, 2008; 283(20): 14072 - 14083. [Abstract] [Full Text] [PDF]