ArticleScience signaling2014
Reliable encoding of stimulus intensities within random sequences of intracellular Ca2+ spikes.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- Mechanisms underlying spontaneous and evoked calcium responses in oligodendrocyte precursor cells: A modeling investigation.PLoS computational biology · 2026Article
- Stochastic model of IP3-induced Ca2+ spiking of HEK293 cells.PLoS computational biology · 2025Article
- Biological physics to uncover cell signaling.Biophysical reviews · 2025Review
- Amplitude and frequency encoding result in qualitatively distinct informational landscapes in cell signaling.Scientific reports · 2025Article
- Transient frequency preference responses in cell signaling systems.NPJ systems biology and applications · 2024Article
- Cell-cell communication: new insights and clinical implications.Signal transduction and targeted therapy · 2024Review
- Article
- An integrate-and-fire approach to CaBiophysical journal · 2023Article
- Maintenance of hematopoietic stem cell niche homeostasis requires gap junction-mediated calcium signaling.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structural titration reveals CaNature communications · 2023Article
- Modeling IPBiophysical journal · 2023Article
- An integrate-and-fire approach to CaBiophysical journal · 2023Article
- Computational investigation of IPScientific reports · 2023Article
- Modeling Calcium Cycling in the Heart: Progress, Pitfalls, and Challenges.Biomolecules · 2022Review
- Kramers Rate Theory of Pacemaker Dynamics in Noisy Excitable Media.Physical review letters · 2022Article
- High rates of calcium-free diffusion in the cytosol of living cells.Biophysical journal · 2021Article
- KRAP tethers IPNature communications · 2021Article
- Highly localized intracellular CaeLife · 2021Article
- Fractional response analysis reveals logarithmic cytokine responses in cellular populations.Nature communications · 2021Article
- Improved bounds on entropy production in living systems.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
9 authors.
Funding
Abstract
Ca(2+) is a ubiquitous intracellular messenger that regulates diverse cellular activities. Extracellular stimuli often evoke sequences of intracellular Ca(2+) spikes, and spike frequency may encode stimulus intensity. However, the timing of spikes within a cell is random because each interspike interval has a large stochastic component. In human embryonic kidney (HEK) 293 cells and rat primary hepatocytes, we found that the average interspike interval also varied between individual cells. To evaluate how individual cells reliably encoded stimuli when Ca(2+) spikes exhibited such unpredictability, we combined Ca(2+) imaging of single cells with mathematical analyses of the Ca(2+) spikes evoked by receptors that stimulate formation of inositol 1,4,5-trisphosphate (IP3). This analysis revealed that signal-to-noise ratios were improved by slow recovery from feedback inhibition of Ca(2+) spiking operating at the whole-cell level and that they were robust against perturbations of the signaling pathway. Despite variability in the frequency of Ca(2+) spikes between cells, steps in stimulus intensity caused the stochastic period of the interspike interval to change by the same factor in all cells. These fold changes reliably encoded changes in stimulus intensity, and they resulted in an exponential dependence of average interspike interval on stimulation strength. We conclude that Ca(2+) spikes enable reliable signaling in a cell population despite randomness and cell-to-cell variability, because global feedback reduces noise, and changes in stimulus intensity are represented by fold changes in the stochastic period of the interspike interval.
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