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J. Biol. Chem. 277 (52): 50226-50229

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

Dampening of Cytosolic Ca2+ Oscillations on Propagation to Nucleus*

Pablo ChameroDagger , Carlos Villalobos§, María Teresa Alonso, and Javier García-Sancho

From the Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Departamento de Fisiología y Bioquímica, Facultad de Medicina, E-47005 Valladolid, Spain

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+]c increases. Thus, encoding of the Ca2+ signal may allow differential control of Ca2+-dependent mechanisms located at either the cytosol or the nucleus.

* This work was supported by a grant from the Spanish Ministerio de Ciencia y Tecnología (MCyT; BFI2001-2073).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Holds a predoctoral fellowship from the Basque Government.

§ Fellow of the Ramón y Cajal Program of MCyT.

To whom correspondence should be addressed: IBGM, Dept. Fisiología, Facultad de Medicina, E-47005 Valladolid, Spain. Tel.: 34-983-423085; Fax: 34-983-423588; E-mail:

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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