Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Encoding of stimulus intensities by sequences of Ca2+ spikes
Kevin Thurley, Stephen C. Tovey, Gregor Moenke, Victora L. Prince, Abha Meena, Andrew P. Thomas, Alexander Skupin, Colin W. Taylor, Martin Falcke

Last modified: 2014-06-09


Ca2+ is a ubiquitous intracellular messenger. Extracellular stimuli often evoke sequences of Ca2+ spikes, and it is suggested that spike frequency may encode stimulus intensity. However, the timing of spikes is random because each interspike interval (ISI) has a large stochastic component. We also find that average ISI vary considerably between cells. Can individual cells reliably encode stimuli when Ca2+ spikes are so unpredictable? Analysis of Ca2+ spikes evoked by receptors that stimulate formation of inositol 1,4,5-trisphosphate (IP3) reveals that signal-to-noise ratios are improved by slow recovery from global feedback inhibition and that they are robust against perturbations of the signalling pathway. Despite variability in the frequency of Ca2+ spikes between cells, steps in stimulus intensity cause the stochastic period of the ISI to change by the same factor in all cells. These fold-changes reliably encode changes in stimulus intensity, and they entail an exponential dependence of average ISI on stimulation strength. We find the latter to apply to different cells, stimuli and stimulation intensities. We conclude that Ca2+ spikes allow reliable signalling even on single cell level despite temporal randomness and large cell-to-cell variability, and that stimulation controls the average stochastic part of ISI with an exponential concentration response relation.