Multi-scale data-driven modeling and observation of calcium puffs

Abstract The spatiotemporal dynamics of elementary Ca2+ release events, such as “blips” and “puffs” shapes the hierarchal Ca2+ signaling in many cell types. Despite being the building blocks of Ca2+ patterning, the mechanism responsible for the observed properties of puffs, especially their terminat...

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Bibliographic Details
Published in:Cell calcium (Edinburgh) 2012-08, Vol.52 (2), p.152-160
Main Authors: Ullah, Ghanim, Parker, Ian, Mak, Don-On Daniel, Pearson, John E
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Blips
Ca2+ signaling
Calcium - metabolism
Calcium Signaling
Endoplasmic Reticulum - metabolism
Inositol 1,4,5-Trisphosphate Receptors - metabolism
Ion channel
IP3R
Kinetics
Models, Biological
Puff termination
Puffs
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Summary:Abstract The spatiotemporal dynamics of elementary Ca2+ release events, such as “blips” and “puffs” shapes the hierarchal Ca2+ signaling in many cell types. Despite being the building blocks of Ca2+ patterning, the mechanism responsible for the observed properties of puffs, especially their termination is incompletely understood. In this paper, we employ a data-driven approach to gain insights into the complex dynamics of blips and puffs. We use a model of inositol 1,4,5-trisphosphate (IP3 ) receptor (IP3 R) derived directly from single channel patch clamp data taken at 10 μM concentration of IP3 to simulate calcium puffs. We first reproduce recent observations regarding puffs and blips and then investigate the mechanism of puff termination. Our model suggests that during a puff, IP3 R s proceed around a loop through kinetic states from “rest” to “open” to “inhibited” and back to “rest”. A puff terminates because of self-inhibition. Based on our simulations, we rule out the endoplasmic reticulum ( ER ) Ca2+ depletion as a possible cause for puff termination. The data-driven approach also enables us to estimate the current through a single IP3 R and the peak Ca2+ concentration near the channel pore.
ISSN:0143-4160
1532-1991
DOI:10.1016/j.ceca.2012.04.018