Irregular Ca2+ 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. CONCLUSION: [Ca(2+)](i) oscillations regulate transcription through [Ca(2+)](i) spike amplitude and cumulative spike duration. SIGNIFICANCE: 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.