Differential regulation of nuclear and cytosolic Ca2+ in HeLa cells.
The results reported in this study address the controversial issue that nuclear free Ca2+ ([Ca2+]n) may be regulated independently of cytosolic free Ca2+ ([Ca2+]c). We have measured [Ca2+]n and [Ca2+]c with recombinant aequorin targeted to the nucleus and cytosol in HeLa cells. We found that histamine, ATP, and ionomycin increased [Ca2+]c quantitatively more than [Ca2+]n, although the time course of these changes was similar. The difference between [Ca2+]c and [Ca2+]n depended on the stimulus, and the relative difference between [Ca2+]n and [Ca2+]c was less with ionomycin than with histamine or ATP. After depletion of the internal Ca2+ store, restoration of extracellular Ca2+ resulted in only increased [Ca2+]c without a significant increase in [Ca2+]n. Treatment with cyclopiazonic acid resulted in a delayed increases in [Ca2+]n compared to [Ca2+]c. These differences in both timing and magnitude of nuclear Ca2+ signals confirm that the cell can limit or delay increases in nuclear free Ca2+. Taken with the fact that an inositol phosphate signaling system resides in the nucleus and its envelope, our data support the hypothesis that [Ca2+]n may be independently regulated.
Badminton
M N
MN
Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff, CF4 4XN, United Kingdom.
Campbell
A K
AK
Rembold
C M
CM
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000331:Aequorin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D007211:Indoles; D011994:Recombinant Proteins; D000331:Aequorin; D015759:Ionomycin; D006632:Histamine; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid