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.
Chamero
Pablo
P
Instituto de Biologia y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Cientificas (CSIC), Departamento de Fisiologia y Bioquimica, Facultad de Medicina, E-47005 Valladolid, Spain.
Villalobos
Carlos
C
Alonso
Maria Teresa
MT
García-Sancho
Javier
J
D000313:Adrenal Medulla; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002417:Cattle; D002467:Cell Nucleus / Q000502:physiology*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000502:physiology; D003600:Cytosol / Q000378:metabolism*; D004058:Diffusion; D009685:Nuclear Envelope / Q000502:physiology; D009991:Oscillometry; D016716:PC12 Cells; D010673:Pheochromocytoma; D010902:Pituitary Gland; D051381:Rats