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Apparently Random Signals Encode Information Reliably
Repetitive Ca2+ spikes occur in many cells in response to stimuli that activate an intracellular signaling cascade that involves Ca2+ released from internal stores. These repetitive spikes are believed to represent the intensity of the stimulus, such that increasing the stimulus increases the frequency of the spikes. But the time between spikes (interspike interval) is random within a cell, and cells in a population exhibit variable spiking frequencies. Thurley et al. performed single-cell Ca2+ imaging of primary liver cells and human embryonic kidney (HEK) 293 cells to examine the properties of Ca2+ spikes in response to extracellular ligands under various conditions. Mathematical analysis revealed that, although the interspike interval had a random element, there was a consistent fold change in this interval across populations of cells responding to different amounts of the ligands. Thus, a common change to a random element enables the cells to properly interpret signal intensity from the frequency of repetitive Ca2+ spikes.