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

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.