| Autor: |
Rüdiger, Sten, Jung, Peter, Jian-Wei Shuai |
| Zdroj: |
PLoS Computational Biology; May2012, Vol. 8 Issue 5, p1-13, 13p, 2 Diagrams, 8 Graphs |
| Abstrakt: |
In many cell types, release of calcium ions is controlled by inositol 1,4,5-trisphosphate (IP3) receptor channels. Elevations in Ca2+ concentration after intracellular release through IP3 receptors (IP3R) can either propagate in the form of waves spreading through the entire cell or produce spatially localized puffs. The appearance of waves and puffs is thought to implicate random initial openings of one or a few channels and subsequent activation of neighboring channels because of an ''autocatalytic'' feedback. It is much less clear, however, what determines the further time course of release, particularly since the lifetime is very different for waves (several seconds) and puffs (around 100 ms). Here we study the lifetime of Ca2+ signals and their dependence on residual Ca2+ microdomains. Our general idea is that Ca2+ microdomains are dynamical and mediate the effect of other physiological processes. Specifically, we focus on the mechanism by which Ca2+ binding proteins (buffers) alter the lifetime of Ca2+ signals. We use stochastic simulations of channel gating coupled to a coarse-grained description for the Ca2+ concentration. To describe the Ca2+ concentration in a phenomenological way, we here introduce a differential equation, which reflects the buffer characteristics by a few effective parameters. This non-stationary model for microdomains gives deep insight into the dynamical differences between puffs and waves. It provides a novel explanation for the different lifetimes of puffs and waves and suggests that puffs are terminated by Ca2+ inhibition while IP3 unbinding is responsible for termination of waves. Thus our analysis hints at an additional role of IP3 and shows how cells can make use of the full complexity in IP3R gating behavior to achieve different signals. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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