Journal Article

Calcium release site ultrastructure and the dynamics of puffs and sparks

Hilary DeRemigio, Jeffrey R. Groff and Gregory D. Smith

in Mathematical Medicine and Biology: A Journal of the IMA

Published on behalf of Institute of Mathematics and its Applications

Volume 25, issue 1, pages 65-85
Published in print March 2008 | ISSN: 1477-8599
Published online March 2008 | e-ISSN: 1477-8602 | DOI: http://dx.doi.org/10.1093/imammb/dqn004
Calcium release site ultrastructure and the dynamics of puffs and sparks

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When Markov chain models of intracellular Ca2+-regulated Ca2+ channels are coupled via a mathematical representation of a Ca2+ microdomain, simulated Ca2+ release sites may exhibit the phenomenon of ‘stochastic Ca2+ excitability’ reminiscent of Ca2+ puffs and sparks. Interestingly, some single-channel models that include Ca2+ inactivation are not particularly sensitive to channel density, so long as the requirement for inter-channel communication is satisfied, while other single-channel models that do not include Ca2+ inactivation open and close synchronously only when the channel density is in a prescribed range. This observation led us to hypothesize that single-channel models with Ca2+ inactivation would be less sensitive to the details of release site ultrastructure than models that lack a slow Ca2+ inactivation process. To determine if this was the case, we simulated Ca2+ release sites composed of instantaneously coupled Ca2+-regulated Ca2+ channels whose random spatial locations were chosen from a uniform distribution on a disc of specified radius and compared the resulting release site dynamics to simulations with channels arranged on hexagonal lattices. Analysis of puff/spark statistics confirmed our hypothesis that puffs and sparks are less sensitive to the spatial organization of release sites when the single-channel model includes a slow inactivation process. We also investigated the validity of several different mean-field reductions that do not explicitly account for the details of release site ultrastructure. The most successful approximation maintains a distinction between each channel's substantial influence on its own stochastic gating and the collective contribution of elevated [Ca2+] from neighbouring channels.

Keywords: puff; spark; ultrastructure; calcium

Journal Article.  0 words. 

Subjects: Applied Mathematics ; Biomathematics and Statistics

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