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Particle-based multiscale modeling of calcium puff dynamics

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cam.issuedOnline2016-07-21
cam.orpheus.successThu Jan 30 12:54:27 GMT 2020 - Embargo updated
dc.contributor.authorDobramysl, U
dc.contributor.authorRüdiger, S
dc.contributor.authorErban, R
dc.contributor.orcidDobramysl, Ulrich [0000-0001-9363-654X]
dc.date.accessioned2016-04-27T12:37:06Z
dc.date.available2016-04-27T12:37:06Z
dc.date.issued2016
dc.description.abstract© 2016 SIAM. Intracellular calcium is regulated in part by the release of Ca2+ ions from the endo-plasmic reticulum via inositol-4,5-triphosphate receptor (IP3R) channels (among other possibilities such as RyR and L-type calcium channels). The resulting dynamics are highly diverse and lead to local calcium "puffs" as well as global waves propagating through cells, as observed in Xenopus oocytes, neurons, and other cell types. Local fluctuations in the number of calcium ions play a crucial role in the onset of these features. Previous modeling studies of calcium puff dynamics stemming from IP3R channels have predominantly focused on stochastic channel models coupled to deterministic diffusion of ions, thereby neglecting local fluctuations of the ion number. Tracking of individual ions is computationally difficult due to the scale separation in the Ca2+ concentration when channels are in the open or closed states. In this paper, a spatial multiscale model for investigating of the dynamics of puffs is presented. It couples Brownian motion (diffusion) of ions with a stochastic channel gating model. The model is used to analyze calcium puff statistics. Concentration time traces as well as channel state information are studied. We identify the regime in which puffs can be found and develop a mean-field theory to extract the boundary of this regime. Puffs are possible only when the time scale of channel inhibition is sufficiently large. Implications for the understanding of puff generation and termination are discussed.
dc.description.sponsorshipThis work was partially supported by the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement 239870.
dc.identifier.citationMultiscale Modeling & Simulation : A SIAM Interdisciplinary Journal 2016
dc.identifier.eissn1540-3467
dc.identifier.issn1540-3459
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/255749
dc.language.isoeng
dc.provenanceOA-8172
dc.publisherSIAM
dc.publisher.urlhttps://epubs.siam.org/doi/10.1137/15M1015030
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectintracellular calcium
dc.subjectcalcium puffs
dc.subjectmultiscale modeling
dc.subjectstochastic diffusion
dc.titleParticle-based multiscale modeling of calcium puff dynamics
dc.typeArticle
dcterms.dateAccepted2016-04-08
prism.endingPage1016
prism.issueIdentifier3
prism.publicationNameMultiscale Modeling and Simulation
prism.startingPage997
prism.volume14
rioxxterms.licenseref.startdate2016-04-08
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1137/15M1015030

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