Dampening of cytosolic Ca2+ oscillations on propagation to nucleus

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 and 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.