Calcium signals in the cell nucleus. Strasbourg, France, August 20-23, 1998

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Abstract
The existence of Ca2+ signals at the level of the nucleoplasm has never been a real issue, as the proverbial hermit cited in Shakespeare's Twelfth Night would no doubt have assented. Typical resting [Ca2+]nucleosol is in the 100–300 nM range whereas, upon stimulation, values of 350–1200 nM can be reached depending on experimental conditions. What has long been contentious, however, is the source of these signals. Where does the Ca2+ liberated inside the nucleus come from? A purely cytosolic origin was the accepted tenet until the early 1990s, but this model came to be questioned by reports documenting rises in nuclear Ca2+ levels independently of changes in cytosolic Ca2+ despite the presence of NPCs. Such gradients were initially observed at rest, but progress in technology allowed measurements to be performed in stimulated cells upon the passage of global Ca2+ waves. Yet these studies have also yielded many negative results. The indicators used, fluorescent radiometric dyes or constructs based on the photoprotein aequorin, tend to produce artefacts and have been blamed for the discrepancies (Malviya and Rogue, 1998). These limitations prompted investigators to develop more reliable methods, and the recent development of Ca2+‐sensitive green fluorescent protein (GFP) derivatives fused with calmodulin (cameleons) has raised great expectations. At the workshop, A.Miyawaki (Japan) presented recent data on Ca2+ signals visualized by two‐photon excitation microscopy using improved cameleons (Miyawaki et al., 1999). He expressed optimism that the teething problems (sensitivity to pH and calmodulin concentrations) outlined during the discussion of his presentation would soon be resolved.