Modeling reveals that nuclear calcium changes cannot be explained by diffusion from the cytosol. The top cartoon shows the essential components, channels, pumps, and pores used in the reaction diffusion model of calcium signal generation. The columns below show an atlas view of the calcium distribution on the nuclear surface. A spike was initiated on the outer side of the nuclear envelope (Left), and then we allow for free diffusion of calcium through the nuclear pores to the inner nuclear membrane (Right). Left: We depict channel clusters on the outer nuclear membrane firing and generating a spike over a time period of 0.6 s. The highest concentrations (cyan) correspond to 20 μM. Right: Calcium changes on the inner nuclear membrane, which fail to rise above a maximum of 15 nM and are negligible on average. In our models, diffusion of calcium through the nuclear pores was not sufficient to allow for oscillations to be transmitted from one side of the nucleus to other.