Irregular Ca(2+) oscillations regulate transcription via cumulative spike duration and spike amplitude.
BACKGROUND
[Ca(2+)](i) oscillations are irregular and heterogeneous.


RESULTS
The correlations between NFκB/STAT3-GFP transcription and [Ca(2+)](i) spike amplitude/cumulative spike duration are revealed by simultaneous monitoring in single cells and validated in cell population.


CONCLUSIONS
[Ca(2+)](i) oscillations regulate transcription through [Ca(2+)](i) spike amplitude and cumulative spike duration.


CONCLUSIONS
How irregular [Ca(2+)](i) oscillations control transcription is crucial for understanding biological [Ca(2+)](i) signal-regulated events. Agonist-stimulated [Ca(2+)](i) oscillations are universally irregular in their kinetics. How irregular [Ca(2+)](i) oscillations dynamically regulate agonist-stimulated downstream events has not been studied. To overcome the obstacles of irregularity and heterogeneity of [Ca(2+)](i) oscillations, agonist-stimulated [Ca(2+)](i) signaling and NFκB/STAT3-GFP nuclear translocation were simultaneously monitored in each single cell examined. The cause-effect relationship between [Ca(2+)](i) oscillation parameters and transcriptional activities was validated in cell populations through irregular [Ca(2+)](i) oscillations with varied parameters. The time duration of cumulative [Ca(2+)](i) elevations reaching the threshold [Ca(2+)](i) level for a transcriptional factor activation and [Ca(2+)](i) spike amplitude was found to control agonist-stimulated transcription and gene expression.
Department of Pathophysiology, School of Public Health, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430030, People's Republic of China.
Shanshan
S
Song
Jiansha
J
Li
Liping
L
Zhu
Lei
L
Cai
Qian
Q
Xu
Chen
C
Ling
Yuan
Y
Su
Qinghua
Q
Hu
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002460:Cell Line; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D002118:Calcium