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Orchestrating reliable cell signalling via calcium melodies

last modified Jun 30, 2014 08:59 AM
Work from Colin Taylor's group, and just published in Science Signaling, has provided new insight into how cells use intracellular calcium spikes to encode extracellular signals. ...
Orchestrating reliable cell signalling via calcium melodies

Courtesy of Science Signaling


We find it easier to count black spots on a white background, a digital signal, than to distinguish shades of grey, an analogue signal. Engineers exploit the advantages of digital signals and so do cells. One of the most common ways by which cells respond to their environment is through changes in the intracellular concentration of a tiny charged particle, the calcium ion. Cells work hard to exclude calcium, but lots of extracellular signals,  hormones and neurotransmitters for example, allow calcium to flow briefly back into the cell through tiny pores, each with its own regulated gate. IP3 receptors are the most common of these calcium channels and when they open in response to signals generated by extracellular stimuli they allow calcium to flood into the cell from intracellular stores. By transforming extracellular messages into intracellular calcium signals that regulate cellular activities, IP3 receptors allow cells to respond to their environment.

Within individual cells, the calcium signals evoked by IP3 receptors are presented as calcium spikes, each spike lasting no more than a few seconds before the calcium concentration recovers to its resting level. The frequency of these calcium spikes often increases with stimulus intensity, sustaining a belief that calcium signals are digitally encoded. But, as Thurley et al now report, different cells exposed to identical stimuli respond with very different frequencies of calcium spikes, and within each cell there is a substantial random contribution to the interval between each calcium spike. The latter is unsurprising because each spike is initiated by a small number of IP3 receptor molecules. With such inherent variability, how might cells respond reliably to changes in extracellular stimulus intensity? The new work, which combines experimental and mathematical analyses, demonstrates that changes in extracellular stimulus intensity cause ‘fold changes’ in the random component of the interval between calcium spikes that are similar for all cells, that is the percentage change in this interval is similar for every cell. This suggests that cells might more reliably detect changes in extracellular stimulus intensity if they ignore absolute spike frequencies, and instead read conserved fold-changes in the random component of the interval between spikes. There is an appealing musical analogy. We recognise a melody whether it is played on a cello or violin, even though the pitch is very different. So too with cells responding to extracellular stimuli: the melody (the fold change in the random component of the gap between Ca2+ spikes) conveys the message, not the pitch (the frequency of the calcium spikes).

Read the full paper here...

BBSRC have run a news item

K. Thurley, S.C. Tovey, G. Moenke, V. L. Prince, A. Meena, A. P. Thomas, A. Skupin, C. W. Taylor, M. Falcke,Reliable encoding of stimulus intensities within random sequences of intracellular Ca2+ spikes, Science Signaling (2014)  7, ra59


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