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Dampening of Cytosolic Ca2+ Oscillations on Propagation to Nucleus

J. Biol. Chem., 27 December 2002
Vol. 277, Issue 52, p. 50226-50229
DOI: 10.1074/jbc.C200522200

Dampening of Cytosolic Ca2+ Oscillations on Propagation to Nucleus

  1. Pablo Chamero,
  2. Carlos Villalobos§,
  3. Marı́a Teresa Alonso and
  4. Javier Garcı́a-Sancho
  1. From the Instituto de Biologı́a y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Cientı́ficas (CSIC), Departamento de Fisiologı́a y Bioquı́mica, Facultad de Medicina, E-47005 Valladolid, Spain

Abstract

Ca2+ signals may regulate gene expression. The increase of the cytosolic Ca2+concentration ([Ca2+]c) promotes activation and/or nuclear import of some transcription factors, but others require the increase of the nuclear Ca2+ concentration ([Ca2+]N) for activation. Whether the nuclear envelope may act as a diffusion barrier for propagation of [Ca2+]c signals remains controversial. We have studied the spreading of Ca2+ from the cytosol to the nucleus by comparing the cytosolic and the nuclear Ca2+signals reported by targeted aequorins in adrenal chromaffin, PC12, and GH3 pituitary cells. Strong stimulation of either Ca2+ entry (by depolarization with high K+ or acethylcholine) or Ca2+ release from the intracellular Ca2+ stores (by stimulation with caffeine, UTP, bradykinin, or thyrotropin-releasing hormone (TRH)) produced similar Ca2+ signals in cytosol and nucleus. In contrast, both spontaneous and TRH-stimulated oscillations of cytosolic Ca2+ in single GH3 cells were considerably dampened during propagation to the nucleus. These results are consistent with the existence of a kinetic barrier that filters high frequency physiological [Ca2+]c oscillations without disturbing sustained [Ca2+]cincreases. Thus, encoding of the Ca2+ signal may allow differential control of Ca2+-dependent mechanisms located at either the cytosol or the nucleus.

  • Abbreviations:
    [Ca2+]c
    cytosolic [Ca2+]
    [Ca2+]N
    nuclear [Ca2+]
    NE
    nuclear envelope
    TRH
    thyrotropin-releasing hormone
    cps
    counts per second
    HEDTA
    N-(2-hydroxyethyl)ethylenediaminetriacetic acid
    • Received September 13, 2002.
    • Revision received November 6, 2002.

    Citation:

    P. Chamero, C. Villalobos, M. T. Alonso, and J. Garcı́a-Sancho, Dampening of Cytosolic Ca2+ Oscillations on Propagation to Nucleus . J. Biol. Chem. 277, 50226-50229 (2002).

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