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Modulation of elementary calcium release mediates a transition from puffs to waves in an IP3R cluster model. PLoS Comput Biol 2015 Jan;11(1):e1003965

Date

01/09/2015

Pubmed ID

25569772

Pubmed Central ID

PMC4288706

DOI

10.1371/journal.pcbi.1003965

Scopus ID

2-s2.0-84922253147   20 Citations

Abstract

The oscillating concentration of intracellular calcium is one of the most important examples for collective dynamics in cell biology. Localized releases of calcium through clusters of inositol 1,4,5-trisphosphate receptor channels constitute elementary signals called calcium puffs. Coupling by diffusing calcium leads to global releases and waves, but the exact mechanism of inter-cluster coupling and triggering of waves is unknown. To elucidate the relation of puffs and waves, we here model a cluster of IP3R channels using a gating scheme with variable non-equilibrium IP3 binding. Hybrid stochastic and deterministic simulations show that puffs are not stereotyped events of constant duration but are sensitive to stimulation strength and residual calcium. For increasing IP3 concentration, the release events become modulated at a timescale of minutes, with repetitive wave-like releases interspersed with several puffs. This modulation is consistent with experimental observations we present, including refractoriness and increase of puff frequency during the inter-wave interval. Our results suggest that waves are established by a random but time-modulated appearance of sustained release events, which have a high potential to trigger and synchronize activity throughout the cell.

Author List

Rückl M, Parker I, Marchant JS, Nagaiah C, Johenning FW, Rüdiger S

Author

Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Calcium
Computational Biology
Computer Simulation
Inositol 1,4,5-Trisphosphate Receptors
Models, Biological
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