The topic of nuclear Ca2+ signalling is beset by discrepant observations of
substantial nuclear/cytoplasmic gradients. The reasons why some labs have
recorded such gradients, whilst other workers see equilibration of Ca-cyt(2
+) and Ca-nuc(2+) using the same cells and techniques, is unexplained. Furt
hermore, how such gradients could arise across the NE that possesses many h
ighly-conductive NPCs is a mystery. Although nuclei may have the capacity t
o be autonomous signalling entities, with functional Ca2+ release channels
and an inositide cycle, the balance of evidence suggests that Ca2+ release
on the inner NE does not occur during physiological stimulation. Our work s
uggests that elementary Ca2+ release events originating in the cytoplasm ca
n give rise to Ca-nuc(2+) signals without causing elevation of the bulk cyt
oplasm. Clearly, the many Ca2+ signalling mechanisms that may impinge on Ca
-nuc(2+) will remain a topic of controversy and debate for some time.