Creatine kinase (CK) catalyzes a reversible transphosphorylation react
ion that is believed to play a crucial role in the maintenance and cha
nneling of high energy phosphate in tissues with high energy demands.
In rat brain development, cytosolic (nonmitochondrial) CK levels incre
ase rapidly during the peak period of myelination and remain high in t
he adult. The cellular compartmentation of CK was investigated through
the use of primary cultures of neurons, oligodendrocytes and astrocyt
es. The CK activity in cultured oligodendrocytes, which expressed both
enzymatic and immunocytochemical markers of myelin, was the highest o
f the cell types examined and comparable to levels measured in whole a
dult brain; these observations suggest a role for CK in myelinogenesis
. We found that low density, dividing astrocyte cultures also exhibite
d high B-CK (brain isoenzyme of CK) immunoreactivity, with the nuclear
CK staining being especially intense. We studied these cultured astro
cytes in more detail with respect to their intense nuclear CK immunore
activity. Optical sections of astrocyte nuclei taken with a confocal m
icroscope show that the high B-CK present is actually contained within
the nucleus, with a nucleoplasmic distribution that does not co-local
ize with DNA or RNA. To ascertain whether the high nuclear B-CK in pro
liferating astrocytes correlated with ongoing cell division, we conduc
ted experiments with confluent, nondividing cultures. These results sh
ow that both CK enzyme activity and immunoreactivity are high in the n
ucleus of proliferating astrocytes, and significantly reduced in the n
ucleus of quiescent, nondividing astrocytes. The high level of CK prot
ein and activity in the nucleus of proliferating astrocytes suggests a
role for CK in cell division/nuclear function. We detail a model for
a nuclear creatine-P/CK energy shuttle in astrocytes, which we propose
contributes substantially to astrocyte nuclear function and is likely
present in oligodendrocytes as well.