Nuclear calcium signalling by individual cytoplasmic calcium puffs

It is known that the nucleoplasmic ionised calcium concentration (Ca-n) nuclear functions such as transcription, although the source and nature of the signals which modulate Ca-n unclear, Using confocal imaging, we investigated the subcellular origin of Ca-n signals in Flue-3-loaded HeLa cells. Our data indicate that all signals which increased Ca-n were of cytoplasmic origin. Ca-n was elevated during the propagation of global Ca waves within cells, More strikingly, we found that individual cytoplasmic elementary release events e.g. Ca puffs, evoked by physiological levels of stimulation, caused transient Ca-n increases. Significantly, >70% of all Ca puffs originated within a 2-3 mu m perinuclear zone and propagated anisotropically across the entire nucleus, Due to the relatively slow relaxation of Ca-n transients compared with those in the cytoplasm, repetitive perinuclear Ca puffs were integrated into a 'staircase' of increasing Ca-n. Due to the effective diffusion of Ca in the nucleoplasm, the nucleus served as a 'Ca tunnel', distributing Ca to parts of the cytosol which were otherwise not within the cytoplasmic diffusion radii of Ca puffs, Given the close proximity of the majority of puff sites to the nucleus, it seems that the elementary Ca release system is designed to facilitate nuclear Ca signalling, Consequently, Ca-dependent regulation of nuclear function must be considered at the microscopic elementary level.