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J. Biol. Chem., Vol. 277, Issue 52, 50226-50229, December 27, 2002

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ACCELERATED PUBLICATION
Dampening of Cytosolic Ca²⁺ Oscillations on Propagation to Nucleus^*

Pablo Chamero, 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.

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