Dampening of cytosolic Ca2+ oscillations on propagation to nucleus

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.