Ca 2+ signals may regulate gene expression. The increase of the cytosolic Ca 2+ concentration ([Ca 2+ ] c ) promotes activation and/or nuclear import of some transcription factors, but others require the increase of the nuclear Ca 2+ concentration ([Ca 2+ ] N ) for activation. Whether the nuclear envelope may act as a diffusion barrier for propagation of [Ca 2+ ] c signals remains controversial. We have studied the spreading of Ca 2+ from the cytosol to the nucleus by comparing the cytosolic

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... the nuclear Ca 2+ signals reported by targeted aequorins in adrenal chromaffin, PC12 and GH 3 pituitary cells. Strong stimulation of either Ca 2+ entry (by depolarization with high K + or acethylcholine) or Ca 2+ release from the intracellular Ca 2+ stores (by stimulation with caffeine, UTP, bradykinin or thyrotropin-releasing hormone, TRH) produced similar Ca 2+ signals in cytosol and nucleus. In contrast, both spontaneous and TRH-stimulated oscillations of cytosolic Ca 2+ in single GH 3 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 [Ca 2+ ] c oscillations without disturbing sustained [Ca 2+ ] c increases. Thus, encoding of the Ca 2+ signal may allow differential control of Ca 2+ -dependent mechanisms located at either the cytosol or the nucleus.