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
01/09/2015Pubmed ID
25569772Pubmed Central ID
PMC4288706DOI
10.1371/journal.pcbi.1003965Scopus ID
2-s2.0-84922253147 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
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 SAuthor
Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
CalciumComputational Biology
Computer Simulation
Inositol 1,4,5-Trisphosphate Receptors
Models, Biological
