Paper Info
Title
Particle-Based Multiscale Modeling of Calcium Puff Dynamics
Abstract
AbstractIntracellular calcium is regulated in part by the release of Ca$^{2+}$ ions fromthe endoplasmic reticulum via inositol-4,5-triphosphate receptor (IP$_3$R)channels (among other possibilities such as RyR and L-type calciumchannels). The resulting dynamics are highly diverse and lead to local calcium “puffs” as well as global waves propagating through cells, as observed inXenopus oocytes, neurons, and other cell types. Local fluctuations in the numberof calcium ions play a crucial role in the onset of these features. Previousmodeling studies of calcium puff dynamics stemming from IP$_3$R channels havepredominantly focused on stochastic channel models coupled to deterministicdiffusion of ions, thereby neglecting local fluctuations of the ionnumber. Tracking of individual ions is computationally difficult due to thescale separation in the Ca$^{2+}$ concentration when channels are in the open orclosed states. In this paper, a spatial multiscale model for investigating ofthe dynamics of puffs is presented. It couples Brownian motion (diffusion) ofions with a stochastic channel gating model. The model is used to analyzecalcium puff statistics. Concentration time traces as well as channel stateinformation are studied. We identify the regime in which puffs can be foundand develop a mean-field theory to extract the boundary of this regime. Puffsare possible only when the time scale of channel inhibition is sufficientlylarge. Implications for the understanding of puff generation and terminationare discussed.
Year
DOI
Venue
2016
10.1137/15M1015030
Periodicals
Keywords
DocType
Volume
intracellular calcium,calcium puffs,multiscale modeling,stochastic diffusion
Journal
14
Issue
ISSN
Citations 
3
1540-3459
2
PageRank 
References 
Authors
0.44
5
3
Name
Order
Citations
PageRank
Ulrich Dobramysl120.77
S. Rüdiger241.95
Radek Erban313321.85