Abstract
Calcium puffs are local transient Ca(2+) releases from internal Ca(2+) stores such as the endoplasmic reticulum or the sarcoplasmic reticulum. Such release occurs through a cluster of inositol 1,4,5-trisphosphate receptors (IP3Rs). Based on the IP3R model (which is determined by fitting to stationary single-channel data) and nonstationary single-channel data, we construct a new IP3R model that includes time-dependent rates of mode switches. A point-source model of Ca(2+) puffs is then constructed based on the new IP3R model and is solved by a hybrid Gillespie method with adaptive timing. Model results show that a relatively slow recovery of an IP3R from Ca(2+) inhibition is necessary to reproduce most of the experimental outcomes, especially the nonexponential interpuff interval distributions. The number of receptors in a cluster could be severely underestimated when the recovery is sufficiently slow. Furthermore, we find that, as the number of IP3Rs increases, the average duration of puffs initially increases but then becomes saturated, whereas the average decay time keeps increasing linearly. This gives rise to the observed asymmetric puff shape.